Molecular Bio Ch 3 Proteins

Proteins Fold into a Conformation of Lowest Energy

1. Final folded structure, or conformation, of any polypeptide chain = the one that minimizes its free energy 2. Denature protein: protein renatures into original conformation (with no help) 3. Molecular chaperones help with protein folding; prevent temporarily exposed hydrophobic regions from aggregating

Fibrous Proteins -COMPOSE EXTRA CELLULAR MATRIXES 9CELLS ARE THETERED TO SOMETHING NOT FLOATING AROUND) -Cells SECRETE ECM PROTEINS (component of cell) TO MAKE THE ECM , THEY ASSEMBLE INTO SHEETS OR LONG FIBRILS - BIND CELLS TOGETHER TO FORM TISSUES Ex. Collagen = most abundant ECM protein Unextendable collagen fibrils (top) that have the tensile strength of steel!!! in collagen each individual piece of rope = a subunit-so 3 individual subunits=A TRIPLE HELIX coiled -coil

???? CYTOSKELTAL PROTEINS ?????? Keratin filaments are extremely stable and are the main component in long-lived structures such as hair, horn, and nails α-keratin molecule is a dimer of two identical subunits, a coiled-coil (see Figure 3-9) Coiled-coil regions are capped at each end by globular domains containing binding sites This enables this class of protein to assemble into ropelike intermediate filaments (important for cytoskeleton)

What's So Special About Humans Anyway?? Our chromosomes contain only about 21,000 protein-coding genes (1) Vertebrates inherited nearly all of their protein domains from invertebrates—with only 7% (UNIQUE) of identified human domains being vertebrate-specific!

(2) Each of OUR PROTEINS ARE on average MORE COMPLICATED, however There are nearly 2X AS MANY COMBINATIONS OF DOMAINS FOUND IN HUMAN PROTEINS as in a worm or a fly Example: the trypsinlike serine protease domain is linked to 18 other types of protein domains in human proteins, whereas it is found covalently joined to only 5 different domains in the worm Greatly increases our range of protein-protein interactions THE > LINKING OF DOMAINS TOGETHER THE >COMPLEX OF AN ORGANISM WE CAN CREATE THIS WILL GREATLY INCREASE OUR RANGE OF PROTEIN-PROTEIN INTERACTION

Disordered Proteins TRANSITIONING B/W STATES = DISORDERED IF INTERMEDIATE= IT CAN BE ORDERED Ex. ELASTIN-DISORDER=ESSENTIAL FOR IT'S FUNCTION OPPOSITE=COLLAGEN molecules can reorganize themselves quite readily into diff conformation ex. in the skin, allows it to stretch and then go back to it's original shape Disorder = a very common function in many proteins about 25% stretch = important b/c protein needs correct structure to fulfill it's function

-1/4 (25%) of all eukaryotic proteins can adopt structures that are mostly disordered -Fluctuate rapidly b/w many diff. conformations. protein structure = not always static Ex. CELL SIGNALING -Contain repeated sequences of AA

Why is There Disorder? DISORDER= BENEFICIAL ESSENTIAL FOR IT'S FUNCTION

-Form specific binding sites for other protein molecules that are of ↑ specificity -altered by protein phosphorylation, protein dephosphorylation, or other covalent modifications that are triggered by cell signaling events

Certain Pairs of Domains Are Found Together in Many Proteins Human genome: 1000 immunoglobulin domains, 500 protein kinase domains, 250 DNA-binding homeodomains, 300 SH3 domains, 120 SH2 domains THESE DOMAINS POP UP IN 1000'S OF PROTEINS > COMMON FOR A PROTEIN TO HAVE SEVERAL DOMAINS > 2/3 of all proteins consist of 2 OR > DOMAINS THE SAME PAIR OF DOMAINS OCCUR REPEATEDLY IN THE SAME RELATIVE ARRANGEMENT IN A PROTEIN

1/2 OFF ALL DOMAIN FAMILIES ARE COMMON TO ARCHEA, BACTERIA +EUKARYOTES BUT ONLY about 5% of the 2-DOMAIN COMBINATIONS ARE SIMILARLY SHARED WE ARE VERY DIFF THAN BACTERIA. WHY? B/C MOST OF OUR DOMAIN COMBINATIONS ARE DIFFERENT. OUR COMBINATION OF DOMAINS ARE STRUNG TOGETHER IN A MORE COMPLEX WAY THAN SIMPLER ORGANISMS COMMONLY FING EP1-PHD-PHD-EP2 DOMAINS A WORM = A LITTLE MORE COMPLEX IN A WORK DOMAINS RETAIN THEIR OVERALL FUNCTION+ SHAPE WE SHARE THE SAME DOMAINS WE DON'T STRING THEM TOGETHER IN THE SAME WAY WE HAVE EXTRA DOMAINS AND STRING THEM TOGETHER IN A MORE COMPLEX WAY THAN SIMPLER ORGANISMS DUE TO RESHUFFELING OF DOMAINS SUGGEST: that most proteins containing especially useful two-domain combinations AROSE arose through domain shuffling relatively late in evolution

10 polar -hydrophyllic AA 2 Acidic - AsGlue Aspartic Acid (AsparDic ) Asp D Glutamic Acid Glu E 3 Basic + HArLyK Histidine His H Arginine (ARRRRG) Arg R Lysine (Lyke) Lys K 5 Uncharged Polar Asparagus Serves Three Tyranical Glutons Aspargine (ASparagus greeN) Asn N Serine (SERves) Ser S Threonine (THRee) Thr T Tyrosine (TYRanical) Tyr Y Glutamine (GLuttoNs) GLN Q

10 Nonpolar-Hydrophobic AA GAVLIMP TPC Glycine Gly G Alanine Ala A Valine Val V Leucine Leu L Isoleucine Ile I Methionine Met M Proline Pro P Tryptophan Trp W Phenylanine Phe F Cysteine Cys C

Sequence vs. Structure -STRUCTURE > CONSERVED THAN AA SEQUENCES -CANNOT BE CERTAIN OF FAMILY RELATIONSHIP B/W 2 PROTEINS W/O DET'M 3-DIM STRUCTURES IF DISCOVER A NEW PROTEIN+WANT TO KNOW WHAT IT IS MOST SIMILAR TO YOU CAN DO BEST= BASED ON CHEMICAL INTERACTION A STRING OF AA = >DO MATHEMATICAL MODELING PROGRAM AND PREDICT HOW THE PROTEIN FOLDS AND COMPARE IT TO KNOW STRUCTURES and show how it folds

2 PROTEINS W. > THAN 25% IDENTITY (OVERLAP) IN AA SEQ USUALLY SHARE THE SAME STRUCTURE BIOINFORMATICS COMPARISONS B/W AA STRUCTURES it's not going to be the best predictor if protein x has the similar function. AA SEQ similarities (not nucleotide seq) will give you a clue but won't be the best predictor of whether the functions are similar. but if 25% identity the can prdict that they have similar structure+function

Helix: Common Structure in Biology QUATERNARY HELICAL STRUCTURE = FORMED BY Biological structures are often formed by LINKING SIMILAR SUBUNITS INTO LONG, REPETATIVE CHAINS W. IDENTICAL SUBUNITS, NEIGHBORING SUBUNITS in the chain FIT TOGETHER by adjusting their relative positions TO MINIMIZE THE FREE ENERGY B/W THE CONTACT POINTS

AA FOLDS INTO CONFIRMATION THAT USES THE LOWEST FREE ENERGY= THE MOST STABLE CONFIRMATION

HOW PROTEINS LINK TOGETHER: Covalent Cross-Linkages Stabilize Extracellular Proteins - can either tie together 2 AA in the same protein, or connect diff. PP CHAINS -Disulfide bonds B/W CYSTEIN RESIDUES (S-S bonds) form in the ER by an enzyme that links together 2 pairs of -SH (SULF HYDRYL) groups or cysteine side chains that are adjacent in the folded protein -Do not change the conformation of a protein but act as atomic staples by reinforcing stable structure -S-S bonds are not found intracellularly b/c of reducing agents in cytosol CYSTEIN RESIDUE + AA = THE SAME LEO the lion says GER LOSS OF ELECTRONS = OXIDATION GAIN OF ELECTRONS = REDUCTION CYSTEINE RESIDUE = SAME AS THE AA CYSTEINE

ADJOINING CYSTEIN RESIDUES FUNCT GROUP SH +SH , NO MORE H IT BECOMES A DISULFIDE BOND, THAT WILL HELP STABILIZE THE PROTEIN. IT IS DICTATED BY THE OXIDATION STATE OF THE CELL. CYSTEIN RESIDUES ARE STRONG TARGETS FOR OXIDATION OXIDATION = WHEN THERE= AN EXCESS OF REACTIVE OXYGEN SPECIES/ FREE RADICALLS PRODUCED BY MITOCHONDRIA (SUPER OXIDE , H-PEROXIDE) THEY'RE AT LOCALIZED CONCENTRATION + WILL REMOVE ELECTRON GROUPS, WHEN THEY REMOVE ELCTRONS IT FACILITATES THE FORMATION OF DISULFIDE BONDS. SO YOU'RE GOING FROM 3 CYSTEINE RESIDUES IN A REDUCED ENVIRONMENT NO ELECTRONS ARE REMOVED. AND IN AN OXIDIZED ENVIRONMENT, ELECTRONS ARE REMOVED THAT FACILITATES A BOND FORMATION B/W THE SULFHYDRYL GROUPS- A DISULFIDE BOND IS FORMED TEXT BOOK SAYS THIS CAN ONLY HAPPEN EXTRA CELLULARY (THIS IS ONLY APPLICABLE TO PROTEINS OUTSIDE OF THE CELL) B/C WE HAVE A LOT OF REDUCING AGENTS INSIDE THE CELL , BUT IT'S NOT ENTIRELY ACCURATE B/C THERE ARE VERY LOCALIZED CONCENTRATIONS OF OXIDATIVE ENVIRONMENTS, LITTLE BUSTS WHERE SUPEROXIDE IS PRODUCED, IN THE CELL AND PROTEINS NEARBY THAT REGION IN THE MICROENVIRONMENT WILL UNDERGO THIS. IT DOES HAPPEN IN CERTAIN MICRODOMAINS IN THE CELL. IF PROTEINS NEAR A SOURCE OF ROS THEY MAY FORM DISULFIDE BONDS DISULFIDE BRIDGES TURN ENZYMES ON AND OFF

Importance of proteins -dryweight = >abundant component of he cell -99% of drugs ->designed to target some type -50% target enzyme that facilitate rxns What are proteins composed of? AA=polypeptide backbone = Alpha C, Amino + Carboxyl group+H w. 1 of 20 different attached side chain LONG POLYMERS OF aa LINKED BY PEPTIDE BONDS ALWAYS WRITTEN WITH THE N TERMINUS ON THE LEFT Each protein differs in it's seq + # of AA seq of the chemically different side chains make each protein distinct presented in N-C direction left to right

Anatomy of a protein: -Peptide bonds=condensation rxn b/w AA (removal of H2O) -Side chains =R->chemically different Difference between two ends? Start amino or N terminus=free amino group NH3+ or NH2 End=Carboxyl or C terminus=free carboxyl group COO-/ COOH

β Sheets -Hydrogen-bonding b/w peptide bonds in different strands holds the individual PP chains (strands) together causes the sheet like conformation 2 things can form a parallel strand or an antiparallel strand -Here: adjacent peptide chains run in opposite (antiparallel) directions -AA side chains in each strand alternately project above and below the plane of the sheet

Arrows are pleated regions the H bonds are forming it Yellow = intervening AA that link the sheets together Red Dash= H bond When get formation of domains there is no break in the polypeptide structure

Quaternary Structure Protein SUBUNITS are made up of DIFF. PP CHAINS Interact through binding sites (non-covalent bonds form between each subunit) NOT CONNECTED BY THE PP BACKBONE BUT BY H BONDING + VAN DER WAALSE INTERACTIONS

CRO REPRESSOR PROTEIN (turns off viral DNA) DIMER: 2 SEPERATE SUBUNITS HELD BY HYDROPHOBIC forces + H-BONDS

Some Protein Domains Are Found in Many Diff Proteins EX. SH2 DOMAIN LIKES TO BIND A CERTAIN TYPE OF LIGAND SO FOUND IN SRC KINASE +RECEPTOR PROTEIN MULTIDOMAIN PROTEIN -originated from the ACCIDENTAL JOINING OF DNA SEQ THAT ENCODE EACH DOMAIN, creating a new gene DOMAIN SHUFFELING: ( GENE SHUFFELING FLIP FLOP) many large proteins have evolved through the JOINING OF PREEXISTING DOMAINS IN NEW COMBINATIONS Binding surfaces exist B/W domains! DOMAINS PRESERVE THEIR FUNCTION BUT THE INGREDIENTS OF THE DOMAINS THAT GIVE THE PROTEIN IT'S OVERAL FUNCTION DOMAIN SHUFFELING -at 1 point maybe 1 gene encoded for 1 little protein now gene dupplication +shuffeling to somewhere else in the genome along with other domains that shuffle elsewhere +recombined themselves. when this happened favorably to form a favorable protein, those organisms survived, the nonfunctional proteins died out during natural selection

DOMAIN SHUFFELING EGF=EPIDERMAL GROWTH FACTOR-cell membrane receptor binds diff paraffin factors that sets of a cascade of cell signaling events CHYMOTRIPSIN= DIGESTIVE ENZYME/ SERINE PROTEASE UROKINASE=METABOLIC PROTEIN FACTOR IX PLASMINOGEN same shape=domain in common Domains were recycled in evolution egf + urokinase share the same functional domain DOMAINS HELPFULL IN THE CELL FUNCTIONING HAVE BEEN RETAINED

Proteins Can Be Classified into Many Families ex. SERINE PROTEASES = protein-cleaving (PROTEOLYTIC) ENZYMES -INCLUDES DIGESTIVE ENZYMES chymotrypsin, trypsin and elastase+ several proteases involved in blood clotting Have nearly identical AA-exist in groups together-the AA composition of the protein probably did vary but b/c it was an AA within the same basic or acidic group despite low AA similarities it still retains a similar fiunction It cleaves a protein out of a Serine residue

Different SP have diff. enzymatic activities, each cleaves diff proteins or the Peptide bonds b/w diff types of AA DISTINCT FUNCTION IN AN ORGANISM PART OF THE AA SEQ OF THE PROTEASE PORTION MATCH + 3 DIM CONFORMATIONS, TWISTS +TURNS ARE VIRTUALLY IDENTICAL serine residue has diff residues on either side so protease could have diff recognition sites they can differ in speed of rxn what turns them on

Surface Conformation of a Protein Determines Its Chemistry Chemical groups on surface interact in ways that enhance the chemical reactivity of one or more amino acid side chains 1. Interaction of neighboring parts of the polypeptide chain may restrict the access of water molecules to that protein's ligand-binding sites (water competes for formation of H-bonds) prevents water from getting into the pockets 2. Clustering of neighboring polar amino acid side chains alters reactivity; protein folding forces together a number of negatively charged side chains against their mutual repulsion - making the affinity of the site for a positively charged ion is greatly increased

How do those chemical groups interact to enhance the chemical rxn of the other AA? 1) neighboring parts of the PP chain can restrict water molecules from getting into that pocket. Ex. in pocket there are many H-bonds, if H2O was in the pockets it would compete for the H-bonds. So H2O isusually excluded in the pockets allowing H-bonds to form. 2) a clustering of polar neighboring AA that might alter the reactivity. It's going to force together negatively charged side chains, pocket will then bind a positively charged ion. 3)AA don't work in isolation, i this binding pocket we have ASpartate, Histidine and Serine, right now it's non reactive, but once H-bonding occuring b/w the Histidine +Serine, b/w Aspartate +Histidine, Serrine and Histidine, what that does is remove a proton from Serine, Protons have + charge, so Serine becomes > -, now it become sreactive Serine + can bind a + charged ligand. It's not Serine by itself but the chemical reactivity of the 3 AA together creates a new chemical charge that can bind the +.

The function of the AA is dictated by what group it falls into How it folds How proteins interact w. each other + other molecules The chem structure of the AA in each group drives the functionality Nonpolar-dislike water-will be on inside

If in the same group they likely have the same chemical properties, enzymes overal function = the same

TECHNIQUES: (1) x-ray crystallography + nuclear magnetic resonance (NMR): HELP PREDICT THE 3D shapes of 100,000 proteins Structural biologists concluded : = limited (2000) number of ways in which protein domains fold up (RESTRICTED BY WHICH AA SEQ GIVES US A STABLE CONFIRMATION)

If know the SEQ of a newly discovered gene - you can predict how the encoded protein will FOLD + FUNCTION BASED ON 25% OVERLAP BUT THEN NEED TO DO 2ND STEP OF MATHEMATICAL FOLDING TO PREDICT WITH CERTAINTY WHAT THE FUNCTION IS

HYDROPHOBIC INTERACTION CREATE A CONFORMATION WHERE ALL THE SIDE CHAINS COME TOGETHER hydrophobic core =nonpolar hydrophyllic polar outside = polar AA a molecule with high degrees of differences in electronegativity b/w 2 atoms makes it polar H2O has a dipole= H=+ O=- differences in electronegativity will allow AA to react with H2O

If take a whole string of AA outside of the cell and trow them into a solution, will they fold up? Will chemical bonds form? Yes but it won't be efficient In a cell you have many unfolded proteins, what is going to prevent 2 proteins from agregating together? The hydrophobic regions like to aggregate together during translation before the protein modifications that are made in the ER and Golgi. What is going to prevent 2 diff hydrophobic regions from 2 diff proteins from aggregating together? Life would not exist b/c our proteins would not be functional. CHAPERONES PREVENT PROTEIN AGGREGATES W/O THEM WE WOULD HAVE NO FUNCTIONAL PROTEINS

HOW LIGANDS BIND TO PROTEINS? Proteins either want to bind to other proteins ex. Keard 1 + Nrf2 or they want a little molecule to bind ex. epidermal growth factor binding to the receptor Thyrosine Kinase in some cases it's tight +irreversible and in some reversible, but it has to be specific so we don't have various growth factors floatng around and binding to whatever they want to, they have to be like the lock +key model. Not all enzymes bind to all substrates SEE DRAWING ENZYME X+Y ENZ X WILL ONLY BIND CARROT OR TRIANGLE SHAPED SUBSTRATE, ENZYME Y WILL ONLY BIND1/2 CIRCLE ENZ X JOB IS TO CLEAVE THINGS + ENZ Y ADDS PHOSPHATE GROUPS SO DON'T WANT ENZ X TO BIND SUBSTRATE Y AND CLEAVE IT UP. THEY HAVE SPECIFIC FUNCTIONS AND NEED TO BIND THE RIGHT SUBSTRATE TO GET THAT FUNCTION ACCOMPLISHED. SPECIFICITY =VERY IMPORTANT. SUBSTRATES ARE AN EXAMPLE OF A LIGAND. HOW DO GET THESE LIGANDS TO BIND? THROUGH H-BONDS, ELECTROSTATIC ATRACTIONS, VAN DER WAALSE + HYDROPHOBIC INTERACTIONS. SAME FORCES ALSO BIND PROTEIN TO A LIGAND THAT BINDS PROTEIN TO PROTEIN. TYPICALLY WEAKER BONDS, NOT COVALENT BONDS. IF THEY ARE WEAK, NOT COVALENT AND YOU WANT THEM TO BIND YO WILL NEED MANY OF THEM. eX. OF A BINDING POCKET OF A SERINE PROTEASE, THERE ARE DIFF AA LINING THE POCKET, SERINE, THREONINE, GLUTAMATE, ARGININE SERINE ALL PART OF THE BINDING POCKET AND THE LIGAND = THE CYCLIC AMP IN ORANGE, cAMP IS NOT JUST BINDING TO SERINE BUT TO MANY DIFF AA, SO YOU NEED A MEANING FULL INTERACTION WITH SEVERAL BONDS. HAVE H-BOND BW SERINE +cAMP, SOME ELCTROSTATIC INTERACTION AS WELL. HOW DOES THE LIGAND BINDING SITE HAPPEN? if you have a linear AA then you need folding in a conformation, so you have a pocket where you have a ligand that is going to bind, or another protein that will fit into the pocket. You have AA side chains and before the folding is complete, you want all the functional groups of the AA to turn inward towards the pockets, very important for the conformation. B/C it's where the funct groups are that the interactions will occur/ligands will bind.

Ligand Binding By: -Hydrogen bonds -Electrostatic attractions -Van der Waals attractions -Hydrophobic interactions These bonds are weak (not covalent), so many bonds needed simultaneously for effective binding

Ligand Binding -All proteins bind to other molecules -binding can be very tight; or weak and short-lived -Always shows great specificity, each protein molecule can usually bind just 1 or a few molecules out of the many 1000's of diff. types it encounters

Ligand= a substance bound by protein

DOMAINS HEAVILY FORMED BY β-sheet-ARE GOOD AT BINDING LIGANDS based domains achieved their evolutionary success b/c they provide a convenient framework for the generation of new binding sites or ligands, requiring only small changes to their protruding loops

MANY THINGS ARE GOOD AT BINDING LIGANDS RECEPTOR PROTEINS, ENZYMES Same domain = found in 2 diff proteins: IMMUNOGLOBULIN = AB FORMATION FIBRONECTIN TYPE 3 MODULE= STRUCTURAL PROTEIN

Differences b/w Domain +Subunit SUBUNIT= -LARGER QUATERNARY STRUCTURE, within are DOMAINS, EACH MADE OF DIFF. PP CHAINS several domains in 1 subunit -FOLD INDEPENDENTLY THEN COME TOGETHER -DO NOT RANDOMLY BIND TO ONE ANOTHER UNLESS THEY HAVE A COMMON FUNCTION -DON'T FORM PP BONDS, BUT WEAKER BONDS LIKE H BONDS + ELECTROSTATIC INTERACTION Ex.Hgb: all translated seperately then come together to form the quaternary structure. eX Hgb = MADE UP OF 4 SUBUNITS, 2 ARE IDENTICAL THE OTHER 2 ARE NOT IN AN APPT BUILDING, SUBUNIT = EACH APPT THE ROOMS ARE DOMAINS

Protein domain: -SU ANY CONTINUOUS PART PP CHAIN- from 1 gene -CAN FOLD INDEPENDENTLY from the rest of the protein INTO A COMPACT+ STABLE STRUCTURE -40 - 350 AA -MOD. U- from which larger proteins are built - DIFF DOMAINS=DIFF (FUNCTIONS makes it a domain) -FOUND IN MANY DIFF PROTEINS -ALPHA HELICES+ BETA SHEETS eX. SRC protein kinase= ENZYME THAT ADDS PHOSPHATE. PHOSPORYLATION OF AN ENZYME TURNS IT ON funct in signaling pathways inside vertebrate cells HAS 3 DOMAINS IN 1 SUBUNIT SH2 + SH3 Domain=regulatory funct C-terminal = catalytic DOMAIN PHOSPHATASE REMOVES PHOSPHATE-TURNS ENZYME OFF

@ physiological ph 7 both the Amino and carboxyl group are ionized (have a charge) NH3+ and COO-

Proteins consist exclusively of the L-amino acids L-isomer is exclusively used in mammals

Ligand Binding Site -Cavity in the protein surface formed by a particular arrangement of amino acids -These amino acids can belong to different portions of the polypeptide chain that are brought together when the protein folds -One protein can have several different ligand binding sites -Other parts of the protein act as a handle to position the protein in the cell -Atoms buried in the interior of the protein have no direct contact with the ligand, they form the framework that gives the surface its contours and its chemical and mechanical properties -Small changes to the amino acids in the interior of a protein molecule can change its three-dimensional shape enough to destroy a binding site on the surface

Surface contours must match + many weak bonds

Domains easily integrate into other proteins! 4 FIBRONECTIN TYPE 3 DOMAINS: CONSISTS OF bETA SHEETS +READILY LINK WITH ONE ANOTHER Domains underwent tandem duplication and readily linked with one another Stiff extended domains common in ec matrix molecules and ex sites of cell surface receptors This example is "in-line" N and C terminals at opp ends "Plug-in": SH2 N and C term close together: insertion loop into another domain

THEY ARE NOT 4 SEPERATE PP CHAINS DOMAINS ARE STRUNG TOGETHER ALL IN 1 SUBUNIT =APPARTMENT 4 FIBRONECTIN TYPE 3 DOMAINS =INLINE=CONNECT VIA THE PP BACKBONE SH2 DOMAIN =PLUG IN= IF N+C TERMINUS ARE CLOSE TOGETHER AND LOOP INTO ANOTHER DOMAIN

a typical protein of about 300 amino acids, a cell could theoretically make more than 10^390 (20^300) different PP chains This require > atoms than exist in the universe Only a very small fraction of this vast set of conceivable polypeptide chains would adopt a stable three-dimensional conformation (less than 1/billion)

Why do most form stable conformation? Natural selection They weren't stable +organisms with those conformations didn't survive

PRIMARY = PP chain -of AA connected by PP bonds Secondary STRUCTURE = Alpha helices +Beta Sheets *come together to make domains TERTIARY=1SUBUNIT W. MULTIPLE DOMAINS FUNCTIONAL unit, COMPLEX FOLDED STRUCTURE CONTAINS SEVERAL DOMAINS OF ALPHA HELICES+ BETA SHEETS 1 binds a ligand, 1 binds a cytoskeleton QUATERNARY = SEVERAL SU OR 2 SEVERAL TERTIARY STRUCTURES WEAKLY JOINED TOGETHER- It facilitates its function

protein = made of a lot of alpha and beta sheets and then some conecting loopy regions

α Helix in proteins - cell membranes (transport proteins + receptors) Hydrophobic regions=transmembrane domain -form coiled-coil -> a stable structure:α helices wrap around each other -Elongated proteins/structural proteins : α-keratin, reinforces outer layer of skin + its appendages

vs. β Sheets in protein - cores -produce a very rigid structure