Protein Processing

Question 1

protein maturation via proteolysis

-example

Answer 1

-some proteins must be lysed, or cleaved, in order to become function
-insulin must be lysed
-

Question 2

reducing and oxidizing in processing

-aa example

Answer 2

• the inside of the cell is udually reducing (p53, R groups of cystein) and the outside of the cell is typiclly oxidizing (insulin, R’s=CH2-S-S-CH2)
• when cystein is oxidized it often presents in a disulfide bond formation with another oxidized cystein, these are called a cystine

Question 3

disulfide bonds

Answer 3

impart high stability in proteins

Question 4

why do proteins fold?

Answer 4

to maximize weak, non-covalent forces

Question 5

what are the strong forces holding proteins together

Answer 5

-peptide and disulfide bonds

Question 6

collagen

• definition
• processing
• composition
• solubility, structure
• types and where they are found

Answer 6

• the major protein in the human body
• made in an immature procollagen form containing 1500 aa’s then is lysed down to 1000 aa’s
• the mature protein has 3 polypeptide chains called alpha chains
• ficrous protein that is insoluble in water
• collagen 1: bone, skin, tendon
• collagen 2: reticulum
• the different types have similar bit not identical sequences
• produced from either 1,2, or 3 different genes

Question 7

skin fobroblast cells and collagen

• types made
• composition
• function
• problem

Answer 7

• they make abundant type 3 and 1 collagen
• they compose fibrils and give structure and rigidity to the skin
• problem is that you do not want fiber assembly inside the fibroblast

Question 8

steps in collagen biosynthesis

Answer 8

1: Chain synthesis-pre/pro alpha chain synthesis
2: Hydroxylation -of several prolines and some lysines in a post-translational modification (requires prolyl hydroxylase or lysyl hydroxylase and the cofactor ascorbic acid Vitamin C)
3: Glycosylation-the hydroxylysines are attachment sites for sugar molecules - the 3 pro alpha chains have been translated and modified
4: Disulfide bond formation- three pro alpha chains assemle and disulfide bonds form at the C terminus
5: triple helix formation- by zipper like folding
6: secretion
7: hydrolysis of propeptides- N terminal and C terminal prpeptides cleaved by procollagen peptidase to make collagen alpha chains
8: assembly into fibril- tropocollagen molecules spontaneously assemble into fibril
9: assembly into fiber and formation of cross link- this is between lysines, catalyzed by the enyme lysyl oxidase to make allysine residue

Question 9

scurvy

Answer 9

• caused by improper hydroxylation during collagen synthesis
• this is caused by lack of vitamin C or the enzyme
• causes collagen to be unstable

Question 10

initial folding of collagen

Answer 10

-unlike typical proteins, which fold from N to C, procollagen begins to fold by disulfide bond formation in the C term

Question 11

-prolines in collagen structure

Answer 11

-neighboring prolines cause steric repulsion and an elongated collagen helix (unrelated to the alpha helix)

Question 12

glycines in collagen structure

Answer 12

-allow the chain to pack together

Question 13

conversion of procollagen to tropocollagen is catalyzed by

Answer 13

-enzymes in the extracellular matrix

-

Question 14

collagen and bone formation

Answer 14

-provides matrix for calcium phosphate deposition to make bones

Question 15

osteogenesis imperfecta

Answer 15

• due to a glycine to cystein substitution in the triple helix region of collagen type 1
• heterozygotes are severly effected because proteins with multiple sub units show dominant mutations

Question 16

for have a function protein in many multi-domain proteins…

-this in relation to osteogenesis imperfecta

Answer 16

• all chains must be correct

- this is show in this disease because hets are severely effected

Question 17

ehlers danols syndrome

Answer 17

• heterogeneous group of diseases
• hyperplastic joints and skin hyperextensibility
• can be caused by improper processing of collagen due to lack of a processing enzyme (het usually ok, homo is not; recessive) or a gene defect in the collagen genes (het not ok)

Question 18

transmissible spongiform encephalopathies

Answer 18

• comes from prion deposition in the brain
• two ways of aquiring: inherit or acquire a missense mutation (CJD), coming into contact with the bad form of the protein (new variant CJD)

Question 19

how do good prions go bad

Answer 19

• come into contact with a infectious prion which causes it to fold into the infectious form_
• this gets progpogated at an increased rate as more proteins change their folding and change that of others (zombie proteins)
• exponential increase