Biochemistry Lecture 7 - Fibrous Proteins

Front 1

Collagenases

Back 1

Degrade collagen (which has half life of several years). Part of MMP, which requires Zinc cofactor to allow cell movement in ECM. Dysregulation leads to cancer, cannot degrade collagen.

Front 2

What are the structural roles of collagen?
in the eye?
in tendons?
bone?

Back 2

In eye it is dispersed as a gel as part of the viterous humor of the eye.
In tendons it is bundled in tight parallel fibers - strength.
In bones is arranged to resist mechanical shear.

Front 3

What does one typical collagen molecule consist of?

Back 3

One typical collagen molecule consists of a triple-stranded helix of 3 protein chains.

Front 4

Why is biosynthesis of collagen preformed at procollagen level?

Back 4

Collagen is insoluble, so synthesis begins at soluble collagen (otherwise protein can't leave cell).

Front 5

What is the amino acid composition of collagen and what is the function?

Back 5

Gylcine - found at each 3rd position of a-chain and allows for tight winding of the triple helix.
Proline - are abundant and lead to "kink" in the protein chain, help close winding.
Hydroxyproline residues - help stabilize the triple-helix via H-bonds.
Lysine - used for extracellular covalent cross-linking of different collagen molecules.
Hydroxylysine - allow for addition of sugars (glucose and galactose)

Front 6

pro-a1 and pro-a2

Back 6

These are the only 2 genes for pro collagen. Their combination will generate different types of collagen.

Front 7

What happens after procollagen is synthesized in released into ER?

Back 7

Select proline and lysine residues will be hydroxylated to for hydroxyproline and hydroxylysine.

Front 8

What is the function of hydroxylase and lysyl hydroxylase?

Back 8

They will hydroxylate lysine and proline residues during synthesis and their catalysis requires VITAMIN C.
Deficiency leads to Scury.

Front 9

What is contained at the N-terminal and C-terminal ends of pro-achain of procollagen which are not found in extracellular collagen, and what is there function?

Back 9

Are propeptides which have mainly three functions:
- they are needed in cytosol for the linkage of the correct 3 pro-a chains to each other by disulfide bonds and
- allow efficient winding during triple helix formation and
- keep the formed procollagen soluble
-Are cleaved by enzymes once procollagen is released into extracellular space

Front 10

Why do you need hydroxy proline residues?

Back 10

They are hydroxylated during biosynthesis of procollagen and allow for formation of hydrogen bonds between the 3-a chain forming the trip helix. Will help to stabilize the structure.
They are never glycosylated and hydroxyl group is need for hydrogen bond.

Front 11

Why do we need hydroxylysine residues.

Back 11

They can be used like lysine residues for extracellular covalent cross-linking of collagen to tropocollagen or be glycosylated and add to variety of other collagens.

Front 12

What is the function of lysyl oxidase once the collagen is released into extracellular space?

Back 12

Is extracellular, it oxidativerly deaminates lysine residues and forms allysine residues (aldheyde is cofactor (copper))
Lysyl oxidase is needed for both, collagen and elastin cross-linking to tropocollagen.

Front 13

Deficiency of Vitamin C

Back 13

Leads to scurvy
Is needed for prolyl and lysyl hydroxylase
Results in abormal collagen containing no hydryoxyproline or hydroxylysine
-lead bleeding gums, hemorrhages, and poor wound heeling

Front 14

Ehlers-Danlos Syndromes (EDS)

Back 14

Mutation of pro-a gene chains of collagen.
Can result from hereditary defect to one of the enzymes needed for correct collagen.
- prolyl or lysyl hydroxylase
-lysyl oxidase
-procalalgen peptidases (removes propeptides)

Patients show hypermobility of joints
-fragility of skin and BV (Type III collagen, can be lethal)
-hyperextention of skin

Front 15

Brittle Bone Snydrome (Osteogenesis Imperfecta)

Back 15

Osteogenesis Imperfecta
-another hereditary defect of collagen (AA substitution of glycine)
-defective collagen
-type I is mild
-type II is severe
-type IV most common - normal sclerae

Patients result in weak bones that bend and fracture easily. Blue sclerae, short stature, hearing loss

Front 16

Osteogenisis Imperfect Tarda - OI Type I

Back 16

Mildest Form -
Collagen is of normal quality but formed in insufficient quantities - occurs in early infancy.
-leads to easy bone fractures
- result in blue sclerae
-hearing loss
-normal or near normal height

Front 17

Osteogenisis Imperfecta Congenita - OI Type II

Back 17

Collagen is abnormal and insufficient quantities.
-Most severe
-leads to death in uetero or neonatal due to respiratory problems

Front 18

Elastin

Back 18

Protein in connective tissue with rubber like properties. Found in elastic fibers of tissues that expand and contract.
-highly cross linked
-forms fibers with glycoproteins microfibrils
-Fond in lung, artery wall, ligaments, skin and ECM

Front 19

AA composition of elastin

Back 19

Hydrophilic sequence rich in lysine, alanine (not charged)
Hydrophobic - rich in glycine, valine and proline
-Lysine and proline - not hydroxylated (mostly)

Front 20

Formation of elastin

Back 20

-tropoelastin is secreted into ECM as a highly soluble linear polypeptide
-protein fibrillin acts as a scaffold for tropelastin, which needs to be cross-linked
-lysyl oxidase forms allysine residues, needed for cross-linking and desmosine formation
- formed from microfibril (elastin, glycoproteins, fibrillin)
-Lack of copper- lead to aneurysms

Front 21

Desmosine

Back 21

-yellow collor
-characteristic of elastin that allows to stretch and bend
-Contains 3 allysine and one lysine residue - covalently linked

Front 22

Marfan Syndrome

Back 22

Genetic defect in gene that encodes fibrillin
-results in long limbs, lens dislocation, aortic dilation, pectus excavatum
-results in improper formation of ECM
Arachnodactylyl - long fingers
Pectus excavatum - chest found inside