Chapter 4 - Proteins
the first item in each key is the ________—the Protein Database ID symbol for that particular motif.
"PDB identifier"
organization of proteins based on motifs they contain at the ________ database
"Structural Classification of Proteins"
"beta conformation" =
"beta sheet"
The protein folds when constrained in this
"capped can"!! chaperonins are elaborate protein complexes required for protein folding (of some proteins that don't fold spontaneously on their own)
The overall process is directed by information in the chain and driven by the _______ energetics of weak interaction formation
"dynamic" weak interaction like (like ionic interactions and hydrophobic interactions)
When there is no regular pattern for the psi and phi angles, it is called
"random coil"
NOT all proteins have more than 1 domain
(some just have a single domain)
many proteins can be denatured by (6)
- heat - pH changes (change protein charge—causes electrostatic repulsion) - organic solvents (such as alcohol) - certain solutes (urea) - detergents
Proteostasis is accomplished by the coordination of many different pathways, for (4)
- protein synthesis - folding - re-folding - degradation.
A = _____ nm A= _____ m
0.1 nm 10^-10 m
Repeating unit is a single turn of the helix, extending ____nm , or ____ angstroms
0.54 nm = 5.4 A
Two major groups of proteins based on tertiary structure
1) fibrous proteins 2) globular proteins
what are the three driving forces for protein folding
1. increase in the entropy of the surrounding water (due to release of water molecules when the protein folds) 2. the hydrophobic effect (clustering hydrophobic AA inside the protein) 3. Disulfide bond formation
A score of ______ indicates a probability of 100% that a protein will be disordered.
1.0
Up to ____ of all human proteins may be unstructured, at least in significant part
1/3
from the 80,000 proteins currently with known structures (x-ray), there are only about ______ different folds or motifs (which show up repetitively)
1200
phi and psi are defined as _____ when the polypeptide is fully extended
180
the degree of a β turn
180
"alpha" and "beta" here, in hemoglobin, do not refer to alpha-helices and beta-sheets (secondary structure) --instead, "alpha" and "beta" here are just used to distinguish_____ within a multisubunit protein, regardless of the predominate types of secondary structure within each subunit
2 different kinds of subunits
the coiled-coil is made from
2 strands of alpha-keratin
Proline in position _____ or glycine in position ____ are common in β turns
2, 3
Under physiological conditions, for typical proteins, the difference between the folded and unfolded states can be on the order of ΔG = ____ kJ/mole.
20-65
Tobacco mosaic virus is made up of
2000 identical subunits
A protein family may be widespread in all
3 domains of cell life: Bacteria, Arachaea, and Eurkarya
Each helical turn = ____ amino acid residues.
3.6
hemoglobin (here) = 1st oligomeric (= multisubunit) protein to have its _____ determined
3D structure
the computer program used for this model has been highly successful in predicting the
3D structure of small proteins from their AA sequence
Hsp______interacts with the unfolded protein Hsp____ is complex and triggers ATP hydrolysis --> produces the closed form of the complex
40 70
all ____ atoms of the peptide bond are in plane
6
quaternary structure of a protein
A number of polypeptide chains linked together into assembled subunits
in a folded protein in native conformation, new bonds form between the
AA
in a folded protein in native conformation, new ionic interactions form among the
AA - some attractive, some repulsive
The 3-D structure of a protein is determined by its
AA sequence
constraining the protein within this chamber prevents inappropriate protein aggregation and restricts the possible conformations that a polypeptide chain can explore as it folds this process is _____ dependent
ATP
chaperones bind and release polypeptide by using energy from ____ and _____
ATP hydrolysis and some other proteins
Alpha keratin is rich in _____ residues
Ala, Val, Lue, Ile, Phe (hydrophobic) and Cys
______ is the most likely amino acid to show up in alpha helices.
Alanine - because it is small
It can then assemble slowly into amyloid fibrils, rich in β sheets, which contribute to the characteristic plaques on the exterior of nervous tissue in people with ______ disease
Alzheimer disease.
example of bulky adjacent R groups that destabilize the alpha helix if close together in the chain
Asn, Thr, Ser, Cys
how is a protein able to assume many conformation
Because free rotation is possible around many of the hundreds of bonds within a protein
Constraints affecting the stability of the α Helix 2) _______ of adjacent R groups
Bulkiness
which bonds of an AA can rotate
C-Calpha N-Calpha
ψ for the ____ bond
C-Cα
superhelical twisting: Three Stranded _____Superhelix (right-handed)
Collagen
______: part of a polypeptide chain that is independently stable or could undergo movements as a single entity with respect to the entire protein
Domains
The native conformation is a very LOW _______ state.
ENTROPY - low state of disorder
in a folded protein in native conformation, there are ____ H bonds between water and the protein
FEWER
4-Hydroxyproline function in Collagen
Forces Pro ring into favorable pucker and offers more H-bonds.
The native conformation usually has the lowest
Gibbs Free Energy (G)
When 2 or more β sheets are layered close together within a protein, the R groups of ___ and ____ touch surfaces
Gly and Ala have the smallest R groups
the alpha chain of collagen repeats what three AA
Gly-Pro-HyPro HyPro = 4-hydroxyproline, and uncommon aa
unfolded proteins are bound within pockets in the ______ complex
GroEL
The _______ Chaperonin system of E. coli assists protein folding in an ATP-dependent process
GroEL/GroES
_____ is a "lid" which transiently caps the GroEL pockets
GroES
the hydrogen bonds in an alpha helix occur between
H atom covalently bonded to electronegative N of the peptide bond. and the electronegative carbonyl O atom of the 4th amino acid away from that peptide bond. N—H | | | O
Every peptide bond in the helix participates in
H-bonding
the entropy of the water molecules surrounding the folded protein is
HIGHER - more randomness
conformational entropy of the unfolded polypeptide is noe
HIGHER - lots of disorder
parallel beta sheet
Having the same amino-to-carboxyl (N-C) orientations among the adjacent polypeptide chains in the beta-sheet
A General Theory of Protein Folding: the ______ Model
Hierarchical = orderly sequence of events
the analogous chaperonin system in eukaryotes is called
Hsp60
The cyclic pathway by which chaperones bind and release polypeptides is illustrated for the chaperone proteins
Hsp70 and Hsp40.
_______ is normally maximized in protein structure.
Hydrogen bonding
Proteins fold to the lowest-energy fold in the microsecond to second time scales.How can proteins fold so fast ?
It is mathematically impossible for protein folding to occur by randomly trying every conformation until the lowest-energy one is found (Levinthal's paradox) Search for the minimum is not random because the direction toward the native structure is thermodynamically most favorable
all amino acids in the alpha helix are ____-stereoisomers
L
the entropy of the water molecules surrounding the unfolded polypeptide is
LOW - lots of order
_______ form first ____ form sequently
Local units of 2o structure (ex. α-helices) form first Longer range interactions (helix-helix, etc) form later
______ are cellular systems that assist proteins in the folding process,
Molecular chaperones and chaperonins
φ for the _____ bond
N-Cα
_______ is one of the best available algorithms for predicting the likelihood that a given amino acid residue is in a region of intrinsic disorder, based on the surrounding amino acid sequence and amino acid composition.
PONDR
Constraints affecting the stability of the α Helix 4) ____ and ____ residues destabilize the helix
Pro and Gly pro: N in pro is part of a rigid ring, so N-Calpha bond rotation is not possible, and there is no H bonding to the N gly: too conformationally flexible
the ____ or ____ permit the sharp twisting of the collagen helix
Pro or HyPro
The different AAs have different propensities to participate in alpha-helices due to the properties of their
R groups
that there are hydrophobic interactions because the
R groups are close together
in the alpha helix, R groups
R groups protrude outside
Ribonuclease Refolding Experiment
Ribonuclease is a small protein that contains 8 cysteines linked via four disulfide bonds Urea in the presence of 2-mercaptoethanol fully denatures ribonuclease When urea and 2-mercaptoethanol are removed, the protein spontaneously refolds, and the correct disulfide bonds are reformed The sequence alone determines the native conformation **Quite "simple" experiment, but so important it earned Chris Anfinsen the 1972 Chemistry Nobel Prize
fibroin is rich in what AAs
Rich in Ala and Gly
the H bonds that crosslink adjacent segments of the polypeptide chain in an anti parallel beta sheet is
STRAIGHT
______causes tooth loss, poor wound healing, bone problems, heart failure
Scurvy
protein conformation refers to the
Spatial arrangement of atoms in a protein
this suggest
Suggests an ancient origin Alcohol dehydrogenase from 2 different organisms example
motifs = _____ structures
Supersecondary
______ is more reliably conserved than primary structure (AA sequence)
Tertiary structure conserve structure as well as function
Why is the alpha helix structure so stable and so common??
The alpha-helix makes great use of internal H bonds
peptide bond
The chemical bond that forms between the carboxyl group of one amino acid and the amino group of another amino acid
Proteostasis
The continual maintenance of the active set of cellular proteins required under a given set of conditions
A Protein's Conformation is Stabilized Largely by
Weak Interactions
t turns out that it would take more than 10^77 years to randomly try out all possible conformations --> so protein folding is NOT a
a completely random, trial-and-error process
Secondary structures of globular proteins
a helix B sheet B turn
The turn is stabilized by
a hydrogen bond from a carbonyl oxygen to amide proton three residues down the sequence (amine proton is the 4th AA residue)
oligomeric =
a multimer with just a few subunits
these peptide-bond electric dipoles are aligned/transmitted through the intrachain H bonds of the helix, resulting in
a net overall helix dipole extending along the helical axis
= a folding pattern that can describe
a part of a protein
these partial charges creates
a small electric dipole
globular proteins: polypeptide chains folded into
a spherical or globular shape
which of these amino acids listed below, would most likely be found in the interior of a globular protein?
alanine because it is non polar
Simplest arrangement the polypeptide chain can assume with its rigid peptide bonds is a helical structure.
alpha helix
The ______ can also have both hydrophilic and hydrophobic surfaces
alpha helix
the collagen helix is a unique secondary structure distinct from the
alpha helix
secondary structure of protein
alpha helix and beta pleated sheet
this motif exists in _______, a bacterial toxin that kills a cell by creating a hole in its membrane
alpha-hemolysin
a series of beta-alpha-beta loops, arranged so that the beta strands form a barrel, creates a particularly stable and common motif called the
alpha/beta barrel
on the beta sheet, the R groups
alternate sides of sheet
The numbers indicate the _________ in this 56 residue peptide that have acquired their final structure in each of the steps shown
amino acid residues
diseases involving formation of amyloid fibers due to protein misfolding are called
amyloidoses
Fatty Acid Binding Protein is formed in a large part of_______ beta sheet
anti parallel
fibroin has _____ beta sheets
antiparallel
β turns facilitate tight turns between 2 adjacent strands of _____ β sheets
antiparallel
The ________ side chains shown here play a significant role in stabilizing the amyloid structure, by HYDROPHOBIC effects.
aromatic
Some proteins need some ________ in order to fold:
assistance
the R groups point _____ from axis of helix
away
why is there not much nutritional value in jello?
because is extremely low in many amino acids that are essential to the human diet
Why are prolines common in beta turns?
because peptide bonds involving this cis configuration is amenable to a tight turn.
the H bonds in a parallel beta sheet are
bent at an angle
green fluorescent protein, found in jellyfish has a ______ structure
beta barrel
Example of stable "α+β" motifs
beta barrel structure the alpha and beta regions are somewhat segregated
β-barrel
beta sheets twisted into a barrel shape
____ is another kind of protein secondary structure
beta turns/bends
an example of a simple motif
beta-alpha-beta loop
conformational changes do NOT involve
breaking covalent bonds ex. is rotation about single bonds
Molecular chaperones and chaperonins assist in the protein folding by (3)
by shielding them from unproductive interactions or by providing a protected folding environment or by preventing aggregation of the unfolded protein
intrinsically disordered proteins can act as
can act as scavengers, binding up small molecules and acting as reservoirs or garbage dumps
intrinsically disordered proteins can act as
can act as spacers, insulators, or linkers in larger structures
The intrinsically disordered ______ of p53 protein binds to at least ____ different binding partners and assumes a different structure in each of these complexes.
carboxyl terminus, 4
a denatured unfolded protein has no _____
catalytic activity
the post-translational processing is catalyzed by ________ and requires _____ and _____
catalyzed by prolyl hydroxylase requires oxygen and ascorbate (Vitamin C)
The p53 protein is made up of several different segments. Only the ______ is well ordered.
central domain the amino terminal and carboxyl terminal regions are disordered
the AAs in intrinsically disordered proteins
charged Lys, Arg, Glu, and destabilizing Pro
the beta sheets are NOT held together by
chemical crosslinks
usually, a domain from a large protein will retain its native 3D structure even when
cleaved away from the rest of the protein
the small R groups of Ala and Gly permit an interlocking arrangement of R groups --> results in
close packing of beta sheets
an example of a fibrous protein
collagen
gelatin Jello is derived from _______
collagen
because vitamin C doesn't work --> _______ isn't made --> connective tissue in the body ______
collagen, CT degenerates
β-barrel is a common
complex structural motif like a soda can
Proteins may change _____ as they bind to other molecules or catalyze reactions
conformation
do proteins have conformation or configuration
conformation
at top: the many unfolded states have a high degree of ____ and _____
conformational entropy and high free energy
The protein folding free energy funnel: as folding proceeds, the narrowing of the funnel reflects the decrease in the
conformational space that must be searched as the protein approaches its native state
see formation of α-helix and tertiary structure based solely on physical chemistry of
constituent functional groups. ex of hierarchical model, with orderly sequence of events
the atoms in the center of the alpha-helix are in very close
contact.
The monomers function together in a _____ manner when associated into this tetrameric form - really nice things result.
cooperative
Collagen superhelices are crosslinked side-by-side by _______ bonds between modified amino acids.
covalent
the amino acid sequence contains
covalent bonds
Connections between elements of secondary structure (Connections between β strands in layered β sheets) cannot
cross or form knots remember that these connections lines are still parts of the protein, so they are parts of the polypeptide chain, so they can't just be twisted up as if they were a piece of string
these new disulfide crosslinks exert twist on the bundles of alpha-helical coils in the hair's keratin get
curls!
in a denatured protein, the disulfide cross links are reduced to yield _____ residues
cys
as folding proceeds, ______ in the number of conformational species present =narrowing of the funnel =_______ in entropy and free energy
decrease, decrease
intrinsically disordered proteins: Contain protein segments that lack
definable structure
a loss of 3D structure sufficient to cause loss of function =
denaturation
The positive amino terminus (last 4 AAs) of the α-helix is destabilized by _____and is stabilized by ______
destabilized by positively charged AA residues stabilized by negatively charged AA residues
The very end of the carboxyl-terminal region has multiple binding partners and folds when it binds to each of them; however, the three-dimensional structure that is assumed when binding occurs is ________ for each of the interactions shown, and thus the color of this carboxyl-terminal segment (11 to 20 residues) is shown in a different color in each complex
different
resonance (partial sharing of electrons) in each peptide bond, between carbonyl O and amide N, creates a
dipole
the peptide bond has a strong
dipole moment - Carbonyl O is negative - Amide H is positive
the inactive aggregates accumulate in cells and cause
disease
Proteins folding follows a
distinct path
mercaptoethanol reduces/cleaves the ______ bonds
disulfide
an oxidizing agent to make NEW ______ bonds between Cys pairs will be added
disulfide bonds
keratin's _____ are manipulated in permanent waving
disulfide bonds
the 4 amino acids at each end of the helix
do NOT participate fully in the helix H bonds
if a person inherits a mutation such as substitution with an aromatic residue at a position that favors formation of amyloid fibrils, Alzheimer's disease symptoms can begin at an
earlier age
likely are linked _____
evolutionarily
Association can ______ existing functionality of subunits
expand
even mild vit. C deficiency causes
fatigue, increased respiratory infection, etc
Structures that maximize hydrogen bonding potential are generally ______ in protein architecture
favored
Additional protein molecules slowly associate with the amyloid and extend it to form a
fibril.
alpha keratin is a _____ protein
fibrous
Fibroin is another
fibrous protein
This core is extremely important both in the _____ and ____ of these very compact proteins.
folding and structural stability
humans cannot make vit. C and must obtain it from
food, like citrus scurvy was lethal to humans making long voyages hundreds of years ago
The 180° turn is accomplished over _____ amino acids
four
phi and psi can have any value between -180 and +180, except when
free rotation is prohibited by steric interference between atoms in the polypeptide backbone and the amino acid side chains
protein needs to be folded properly in order to______
function properly
most enzymes, regulatory proteins, transport proteins, immunoglobulins, motor proteins... are
globular
most enzymes are
globular proteins
example of 3 groups that repel each other and would prevent an alpha helix from forming
glu, lys and arg
this motif also exists in ______ proteins...
green fluorescent
all fibrous proteins are insoluble in water because
have a high concentration of hydrophobic amino acid residues
anti-parallel beta sheet
having opposite amino-to-carboxyl (N-C) orientations among the adjacent polypeptide chains in the beta-sheet
Some are called ____ proteins since they are synthesized during periods of _____
heat shock proteins or stress proteins synthesizes during period of stress
these peptide-bond electric dipoles increases as
helical length increases
Protein MISfolding is the basis of numerous
human diseases Type II Diabetes Alzheimer's Disease Huntington's Disease Parkinson's Disease Prion diseases like Mad Cow and CJD
When they are interior there is maximal ______ of polar groups.
hydrogen bonding
Sheet-like arrangement of backbone is held together by _____ bonds between the backbone amides in different strands
hydrogen bonds
Hb subunit is the tetramer with four subunits (2 α chains and 2 β) held together mainly by _______
hydrogen bonds and ionic interactions.
2 aromatics 3-4 residues away from each other is a _______ interaction
hydrophobic
proteins that are not properly folded often have exposed ______ surfaces that render them "sticky," leading to the formation of inactive aggregates
hydrophobic
urea (or organic solvents or detergent) disrupts _____ interactions in the core, and urea also disrupts _____
hydrophobic and H bonds
since R groups alternate sides of sheet, it is possible to make β-sheets with ____ and /or_____ surfaces
hydrophobic and/or hydrophilic (bc R groups could be hydrophobic or hydrophilic)
intrinsically disordered proteins lack a
hydrophobic core
The interior of most globular proteins consists of a _____
hydrophobic core with little or no water present. (Hydrophobic and van der Waal's interactions)
the photo fibril is stabilized mainly by
hydrophobic interactions and disulfide crosslinks
hsps bind to regions of unfolded polypeptides that are rich in ______, preventing inappropriate aggregation
hydrophobic residues
The core of the helix is somewhat
hydrophobic.
The tendency of a given segment of a polypeptide chain to form an alpha-helix depends on the
identity and sequence of amino acid residues within the segment.
Higher order structures formed by specific subunit associations often have new binding, catalytic or regulatory functionality not found in the
individual subunit monomers.
silk is made by
insects and spiders
Typical Globular Protein Tertiary Structure: Most hydrophobic amino acids are on the _____ of the folded protein and may contribute to the hydrophobic core.
inside
Common mechanism: a normally-secreted soluble protein is misfolded and converted into
insoluble extracellular amyloid fibers
amino acids that are far apart in the polypeptide sequence and are in different types of secondary structure may actually
interact with each other within the completely-folded structure of a protein
Polar-noncharged amino acids also tend to appear on the protein surface but may be in the
interior
the hydrophobic AA now buried/ cluster in the
interior of the protein
positive R's often found 3-4 away from negative R's =
ion pair formation positively charged AAs found 3-4 away from negatively-charged amino acids
Human hair is made out of what protein
keratin
the binding of small molecules may affect the interaction between subunits --> causing
large changes in the protein's activity in response to small changes in the concentration of substrate or regulatory molecules
In some cases, the only feasible way to get the required functionality is to form
large multimeric quaternary structures
close packing of the polypeptide chains within the
left-handed supertwist
intrinsically disordered proteins are composed of amino acids whose higher concentration forces...
less-defined structure
secondary structure refers to a
local spatial arrangement (conformation) of the polypeptide backbone
fibrous proteins: polypeptide chains arranged in
long strands or sheets
the conformational entropy of folded protein is
low - lots of order
The α helix has a large
macroscopic dipole moment
stability of a protein refers to its tendency to
maintain a native conformation
the molecular motions of the peptide and the effects of the water molecules were taken into account in
mapping the most-likely paths to the final structure among countless alternatives
The native conformation of most proteins is ______ stable
marginally stable (its tendency to remain folded is marginal)
Chaperones prevent
misfolding
_____ are particularly stable arrangements of 2 or more elements of secondary structure and the connections between them
motifs
Common, regular folding patterns of the polypeptide backbone are stabilized by
multiple non-covalent interactions.
This is because left-handed connections
must traverse sharper angles, are longer, and are harder to form
Some fraction of the molecules released at the end of the cycle are in the
native conformation
An isolated protein has a unique, or nearly unique, stable structural form called the
native fold
there are no _____ bonds or ____ interaction between AA
no H bonds no ionic interactions
the 3 D shape of the formed as the tertiary structure contains _____ bonds
non covalent bonds, weak interactions
these assembled subunits of folded polypeptide chains contain _______ bonds
non covalent bonds, weak interactions
the alpha helix and beta pleated sheet contain ____ interactions
non-covalent bonds, weak interactions
The most important forces in stabilizing the specific functional structure of a given protein are
non-covalent interactions (H bonds, hydrophobic effect, ionic interactions, van der Waals forces).
Very heat-stable proteins of thermophilic bacteria (living in near-boiling water of hot springs) are stabilized by
numerous ion pairs, therefore have very tightly-packed hydrophobic cores
fibrous proteins usually consist of mostly
one type of secondary structure
this 20-65 kJ/mole corresponds to
only a "few" weak interactions holding the whole protein together!.
the R groups of adjacent amino acids protrude from the zigzag structure in
opposite directions create the alternating pattern seen in the side view above
All peptide bonds in the α helix have a similar
orientation
Charged amino acids usually are found on the ______ of the protein. Favorable charge-charge interactions (+/-) may contribute to protein stability.
outer surface
_______ protein is critical in the control of cell division
p53
The planes of the rigid peptide bonds are _____ to the long axis of the helix
parallel
Amyloid-β peptide may take the form of two layers of extended _______
parallel β sheet.
a peptide C-N bond cannot rotate freely because of
partial double bond character - o partial negative charge - H bonded to N has partial positive charge
this influences the _____ of the polypeptide connection between the segments
path
so the partial pos and neg charges of the helix dipole actually reside on the
peptide amino and carbonyl grps near the N-terminal and C-terminal ends of the helix
Peptide conformation is defined by angles
phi & psi: φ and ψ -these are the angles at the intersection of the 2 planes
The planarity of the peptide bond and tetrahedral geometry of the α-carbon create a
pleated sheet-like structure β Sheets
Side chains can be and often are ordered in such a way as to make the helix structure _____ on one side and _____ on the other side
polar , hydrophobic
Negatively charged residues often occur near the ______ end of the helix dipole
positive
OVERALL, the N-terminus is ______and the C-terminus is _______
positive, negative
The negative carboxyl terminus (last 4 AAs) of the α-helix is stabilized by ______ and is destabilized by ______
positively charged AA residues negatively charged AA residues
When 2 or more β sheets are layered close together within a protein, the R groups of the AA residues on the touching surfaces must be
pretty small
The chaperones do not actively promote the folding of the substrate protein, but instead
prevent aggregation of unfolded peptides.
The Ribosome: Ensures correct translation of the genetic code into the protein ______ structure
primary
what is only AA that contains a trans C-N bond
proline
example of "all beta" motifs
propeller
proteins with significant similarity in either primary sequence AND/OR in tertiary structure/function are said to be in the same
protein family
Fibroin
protein in silk
tertiary structure of protein
protein structure is formed when the twists and folds of the secondary structure fold again to from a larger 3D structure
Disordered regions of these proteins can bind to many different
proteins, facilitating interaction with numerous different partner proteins
in the alpha helix conformation, the polypeptide backbone is tightly wound around an imaginary axis drawn longitudinally through the middle of the helix, with the R groups
protruding outward
fibrous proteins function to
provide support, shape, external protection to vertebrates
the Tobacco mosaic virus is an example of a _____ structure
quaternary
this is an example of _____ structure (multiple subunits assembled together) Hb has 4 subunits together
quaternary
Rigid peptide bonds limit the
range of conformations possible for a polypeptide chain.
the three steps to form wavy hair
reduce, curl, oxidized
Association of______protein subunits can form structural, protective, or dynamic quaternary aggregates
repetitive
all 6 atoms of the peptide bond are in plane due to
resonance between the carbonyl oxygen and the amide nitrogen
There are lots of turns or loops in compactly-folded, globular proteins where the polypeptide chain needs to _____ in order to do the folding.
reverse direction
the expt showed that the denaturation of some proteins is
reversible
The ________ is made up of dozens of protein subunits, plus several RNA molecules, all associated together!
ribosome
all proteins begin their existence on a ________, as linear sequence of amino acid residues
ribosome
Collagen superhelix is _____ handed
right
Connections between strands of a parallel β-sheets are almost always
right-handed
Helical twist is _______in most proteins
right-handed -clockwise
the peptide bond is ___ and ____
rigid and planar
a peptide C-N bond cannot
rotate freely
the primary structure is NOT totally static
rotational conformational changes around single bonds
even quite different AA sequences might fold up into the
same type of motif
without vitamin C, you get the disease _____
scurvy
A motif is a structural element falling between ____ and _____ structure
secondary and tertiary
Small regions of _______ are assembled first and then gradually incorporated into larger structures.
secondary structure
in eukaryotes, disulfide bonds are found primarily in
secreted, extracellular proteins
the small depressions along the funnel's sides =
semistable intermediates
primary structure of protein
sequence of amino acids (amino acid residues)
globular proteins: often contain ______ types of secondary structure and a typically water or lipid-soluble
several
The beta (β) conformation organizes polypeptide chains into
sheets zigzag polypeptide chains can be arranged side-by-side to form this pleated structure:
in each fibrous protein, the fundamental structural unit is a
simple repeating element of secondary structure most enzymes are globular
Complex structural motifs are often built up from
simpler, often repetitive motif elements
sometimes a ______ may comprise the entire protein
single large motif
at bottom of funnel, an ensemble of folding intermediates has been reduced to a _____.
single native conformation (or a few)
The most stable configuration for the β-sheet is a
slight twist. this is why the beta-barrel can exist
(fibroin) silk is ____ and _____
soft and flexible
Constraints affecting the stability of the α Helix 3) interaction between AA side chains spaced
spaced 3 0r 4 residues apart
the 3 D shape of the protein at the tertiary structure contains
spatial arrangement of atoms
Often each domain has a
specific, related function
globular proteins have polypeptide chains folded very compactly into a ____ shape
spherical or globular
globular proteins
spherical, water-soluble proteins.
the beta conformation is most ______ when the individual segments are twisted slightly in a right-handed sense
stable
further assembled into collagen fibrils: tensile strength greater than that of
steel wire (of the same diameter)!
the fact that the beta sheets are held together by weak interactions imparts both
strength and flexibility
this super twisting of the filaments amplifies the
strength of the overall structure (like if you twisted 2 ropes together)
when alpha helices and beta sheets occur together in proteins, they are generally found in different
structural layers
proteins have common
structural patterns
The function of a protein depends on its
structure.
Constraints affecting the stability of the α Helix 1) electrostatic attraction or repulsion between
successive (close together) AA residues with charged R groups
Beta turns are often found near the ______ of a protein
surface
High tensile strength with no stretch - used in
tendons, bone matrix, cartilage
fibrous proteins have pretty simple
tertiary structure
part of the intermediate filament family of proteins, like
the IFs in the cytoskeleton
the Anfinsen experiment (using ribonuclease) provided the 1st evidence that
the aa sequence contains all the info required to fold the chain into its native, 3D (tertiary) structure
they are in different structural layers because
the backbone of protein segment in beta sheet cannot readily form H bonds to an alpha-helix aligned with it
silk cloth does not stretch because
the beta sheet is already a highly extended conformation
at the bottom, Stabilization of structure by _____, causes _____entropy and free energy
the hydrophobic core, H-bonds, ionic interactions, Van der Waals (VDW) interactions decreased
when urea and mercaptoethanol are removed,
the native tertiary structure, catalytically active state returns and the disulfide cross links are reformed
since the The sequence alone determines the native conformation....
the primary structure of the protein (amino acid sequence) contains the "molecular instructions" for 3D folding and tertiary structure.
protomer =
the repeating structural unit in a multimeric protein (would be 1 alpha plus 1 beta subunit in hemoglobin)
but structure is flexible because
the sheets are held together by numerous weak interactions rather than by covalent disulfide bonds (chemical crosslinks)
______, the folding process can be viewed as a free-energy funnel
thermodynamically
of all of the enormous number of possible ways to fold up even a simple protein, the "one" native conformation is the
thermodynamically most stable
the C-N bond all all but one AA is
trans
hsps also block the folding of certain proteins that must remain unfolded until they have been
translocated across a membrane
this chaperonin complex contains _______ in which proteins can fold in a relatively isolated environment.
two cavities
since these proteins are stabilized by these factors, they are less susceptible to
unfolding
Side chains protrude from the sheet alternating in
up and down direction
denaturing conditions
urea + mercaptoethanol
if gly gets substituted by a bulkier AA via a genetic disease,
very bad symptoms or lethality results due to the deleterious effects on collagen structure
the aa composition + supertwists of collagen =
very close packing = very strong!!
Association of repetitive coat protein subunits in the protects
viral RNA core.
un an unfolded polypeptide, hydrophobic AA are exposed to
water
in an unfolded polypeptide, hydrogen bonds occur between
water and the peptide
fibroin Forms bets sheets which are stacked and held together by
weak interactions (H bonding and van der Waals between sheets)
these factors of denaturation disturbs ______ interactions
weak non covalent, covalent bonds remain intact
the H bonds in a parallel beta sheet are ______ than the H bonds in anti-parallel sheets
weaker
intrinsically disordered proteins can inhibit the action of other proteins by
wrapping around their protein targets
intrinsically disordered proteins cannot be crystallized for structure determination by
x-ray crystallography
______ different protein families in the PDB
~4000
About ____of all AA residues found in proteins are found in alpha-helices
¼
Myoglobin is a small oxygen binding protein composed primarily of
α-helices
occur frequently whenever strands in β sheets change the direction
β turns
In a small number of the molecules, before folding is complete, the ______ regions of one polypeptide associate with the same region in another polypeptide, forming the nucleus of an amyloid.
β-sheet
