Exam 2: Structural Proteins: Fibrous

how to make hydroxyproline

proline is hydroxylated to hydroxyproline in an enzymatic reaction that occurs when the collagen polypeptide is synthesized

Repeat sequence in silk fibroin

(Gly-Ala-Gly-Ala_Gly-Ser)n

Coiled Coils

(keratin) formed when 2+ a-helices self assemble by winding around each other to form a left-handed supercoil -dimers, trimers, and tetramers are the most common structures -larger coiled coils of up to 7 helices can be designed

Collagen related diseases

- scurvy - lathyrism -brittle bone disease - ethler-danlos syndrome

Silk Fibroin applications

-3D printing -electrospinning -hydrogels -sponges -bone tissue engineering -tissue regeneration as bio scaffolds

Elastin structure

-It has an irregular or random coil conformation made up of 830 amino acids -Elastin is made by linking many soluble tropoelastase protein molecules, in a reaction catalyzed by lysyl oxidase to make cross links -the amino acid responsible for these cross links is lysine -the formed structures are specific to elastin and are named desmosine and isodesmosine -desmosine forms cross links and binds 4 adjoining elastin chains by forming intermolecular linkage

Structural Proteins

-Keratin: hair and nails -collagen fibers: support many organs, most abundant protein in our body, found everywhere -myosin and actin: make up the bulk of muscle -enzymes: proteins that act as organic catalysts to speed chemical reactions within cells -insulin protein: hormone that regulates glucose content of blood -hemoglobin: transports oxygen in blood -proteins embedded in the plasma membrane: have varied enzymatic and transport functions

Keratin structure and hair

-Keratins, particularly aa-keratin, Have long sequences of amino acids (often more than 300) which forms a helical structure. -Pairs of these helical structures then coil about each other in a left-handed coiled coil structure. These are then attracted to another coiled coil so two keratin helices will stick together -These four chain structures then associates with another four-chain structure to form the hair filament. One of the amino acids which makes up these chains, is cysteine which has a sulfur group which forms S-S bonds on other coiled coils -the more interactions a filament has with another filament, the more tightly coiled the coiled coil becomes

Elastin

-Less abundant, rubbery protein compared to collagen. -It is found in ligaments, artery walls, lungs and muscles. -It has a high content of glycine -Some of the amino acids include glysine, valine, alanine, and proline.

Knobs in Hole Model

-The positions of the side chains along the surface of the cylindrical alpha helix is projected onto a plane parallel with the helical axis of both alpha helices of the coiled coil -Decide change positions of the first helix, the knobs, superimpose between the side chains positions in the second helix, the holes

How hair curling works

-change in location of bonds causes curling of the hair 1). Straight hair strans have vertically linked disulfide bridges 2) use waving lotion, and disulfide links are reduced to thiol (-SH) groups so the hair strands can be separated from each other 3). Hair strands are now free 4). Curling reorients the strands and the thiol groups (still reduced) 5). H2O2 oxidises some of the adjacent thiol groups to disulfide links to fix new orientation of the hair strands.

shape of hair follicle

-determines the structure of the hair strand because it determines how hair emerges from the scalp -when it emerges in a bent shape, it faces a lot of tension from the scalp, which causes it to bend in the shape of the follicle to form

How are cross links formed?

-elastin has a repeating domain structure consisting of lysine-containing sequences that populate crosslinking sites and hydrophobic sequences that contribute to elastic recoil. -the epsilon-amino group of lysine residues in alanine rich (KA) or Pro-rich (KP) sequences are oxidized by the enzyme lysyl oxidase resulting in bi-functional and tetra functional crosslinks.

Desmosine and Isodesmosine

-formed from the covalent linkage of four lysine amino acids in elastin. A 6-membered ring is shared between the lysines.

collagen

-many different types of collagen proteins exist, and taken together, these are the most abundant proteins in an animal -collagen is a fibrous protein that plays a major structural role in the extracellular matrix and is a major component of bone, teeth, cartilage, and tendon -collagen is the molecular "glue" that holds tissues together

Keratin

-polypeptide chains of keratin are arranged in parallel sheets held together by H bonding 1). all the domains in a keratin monomer, monomers self assemle into alpha helix 2). 2 keratin monomers form a parallel dimer by the winding of their alpha helical structure into a coiled coil in the same direction 3). 2 dimers join side-by-side in a staggered anti-parallel orientation to form a bidirectional tetramer 4). Tetramers are linked in a head-to-tail fashion to yield linear chains, i.e. protofilaments 5). Groups of two protofilaments intertwine to form protofibrils, and groups of four protofibrils intertwine to produce the 10 nm filament (See diagram in notes)

Fibroins + their important structural features

-proteins of silk -produced by insects and spiders -polypeptide chains are predominantly in the B conformation -Fibroins are rich in Ala and Gly residues, permitting close packing of (antiparallel?) B sheets and an interlocking arrangement of R groups -The overall structure is stabilized by extensive H bonding between all peptide linkages in the polypeptides of each B sheet and by the optimization of van der Waals interactions between sheets -The structure is flexible because the sheets are held together by weak interactions rather than by covalent bonds

fibrous proteins

-silk fibroin -keratin a lot of fibrous proteins have repeat sequences, it gives them regular structure and strength

quaternary structure of collagen

-triple helix -trimeric collagen molecules are the quaternary structural unit of collagen fibers -formed in the endoplasmic reticulum, where three collagen chains wrap around each other to form a right0handed triple helical structure approximately 3,000 Å long and 15 Å wide -the initial twirl is left handed, then another is added that is left handed, and the third is right handed. This causes it to become like a knot, and it cannot be broken up easily, which is why it is so prominent in the body -Stabilizing hydrogen bonds form between backbone amino (-NH) groups of glycine residues and the backbone oxygen atoms of amino acid residues in the other chains

Type III Collagen

Found in myriad in human muscles, uterus, blood vessels and intestines. It is commonly mix with type one collagen to help with skin and gut healing. Also helps with the stretching and hydration of the skin -found alongside type I collagen (though in smaller amounts) -supports skin and bone health -also is a part of arterial walls and important for cardiovascular health -beef based collagen is a popular source

Collagen vs Elastin

Collagen is much more structured and rod like whereas the elastic fiber is relaxed and like a random coil. Even in its more ordered/stretched form elastin is not as structured. -both are affected by time and the elements, and diminished levels of them cause skin to wrinkle.

Type I collagen

Due to abundance in tendon rich tissue, these types of collagen helps tremendously with rebuilding muscles, bones, eyes, spine, and other tendons -most common type -makes up 90% of our hair, skin, nails, organs, bones, and ligaments -supports healthy, youthful looking skin -marine collagen is a popular source

fibrous vs globular examples

F: collagen and keratin G: hemoglobin, insulin, catalase.

fibrous vs globular stability

F: less sensitive to changes in heat and pH G: more sensitive to changes in heat and pH

fibrous vs globular shape

F: long and narrow G: rounded/spherical

fibrous vs globular solubility in water

F: mostly insoluble G: mostly soluble

fibrous vs globular sequence of amino acids

F: repetitive amino acid sequence G: irregular amino acid sequence

fibrous vs globular role

F: structural (strength and support) G: functional (catalysts and transport)

defining characteristic of a coiled coil

Knobs-into-holes packing regime

The role of glycine in collagen

The conservation of glycine in every third position is critical to proper collagen assembly -Collagen triple helices are transported from the endoplasmic reticulum to the extracellular space, where they assemble in a staggered formation to form collagen fibers. -The assembly of collagen fibers is largely driven by hydrophobic interactions between triple helical molecules. -Collagen's well packed, rigid structure is responsible for its tensile strength. -The twist in the helix cannot be pulled out under tension because its component polypeptide chains are twisted in the opposite direction

Secondary structure of collagen

The conserved collagen triplet repeats readily form a stable and narrow left-handed helix, which defines the secondary structure of collagen

Type IV and V Collagen

This collagen is required for neurons, and to create the placenta in pregnant women. It supplies nutrients and oxygen to the fetus. Type V also helps create hair and cell surfaces. Type 4: -less abundant in the body and less common in supplements -Type V forms cell membranes and placenta tissue -Type X helps forms bones -typically found in multi collagen protein supplements

Type II Collagen

This tape mainly makes up all the protein molecules in cartilage, the connective tissue around bones and joints. Very beneficial for arthritis -helps build cartilage and maintain our gut lining -support joint and digestive health, promotes immune function'-often made from chicken (found in chicken soup)

Types of Collagen

Type I Type II Type III Type IV and V

Ligaments and tendons

both have elastin -tendons bind muscle to bone -ligaments bind bone to bone

waving lotion

ammonium thioglycolate -ammonium makes it soluble, so when you put it in hair it dissolves

brittle bone disease

caused by mutation of Type I collagen

lethyrism

caused due to reduced cross linking of collagen fibers causing abnormalities in bone, joints, etc

heptad repeats

comprise 7 amino acids, denoted "abcdefg" -hydrophobic residues fall at the "a" and "d" positions, giving rise to a (HPPHPPP)n pattern -placing hydrophobic amino acids three and four residues apart means they end up on the same face of the helix, and hydrophobic face is the driving force for coiled coil formation

fibrous vs globular proteins

differ in shape, role, solubility, sequence of amino acids, stability

where is keratin found?

fibrous structural protein of hair, nails, horn, hoofs, wool, feathers, and of the epithelial cells in the outermost layers of skin

driving force for coiled coil formation

hydrophobic face formed by heptad repeats

scurvy

hydroxy proline production decreases as a result of a Vitamin C deficiency

Ethler Danlos syndrome

hyperextensibility of the joints, almost like rubber -caused due to abnormal activities of collagen processing enzymes or amount of type of collagen synthesized

Primary Structure of Collagen

largely composed of triplet repeat sequences (1000s and 1000s of repeats) in which: -the first residue is usually the small residue Gly (or Ala) -the second is usually Pro -the third is usually hydroxyproline. Hydroxyproline is good because it can H bond, but it is also rigid like proline

Silk Fibroin and B sheets

silk is made of long fibroin proteins a). that have a repeating molecular structure. These proteins bond together into B sheets b). which then stack together c). to form materials with high strength and toughness

biosteel

spider webs, one of the strongest biomedical substances

knobs into holes packing

the side chains of hydrophobic residues act as "knobs" and pack into "holes" formed by four residues from a neighboring helix. -the majority of coiled coils also possess a repetitive sequence pattern, known as a heptad repeat