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Flashcards in Protein Processing Deck (19):

protein maturation via proteolysis

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


reducing and oxidizing in processing
-aa example

-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


disulfide bonds

impart high stability in proteins


why do proteins fold?

to maximize weak, non-covalent forces


what are the strong forces holding proteins together

-peptide and disulfide bonds


-solubility, structure
-types and where they are found

-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


skin fobroblast cells and collagen
-types made

-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


steps in collagen biosynthesis

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



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


initial folding of collagen

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


-prolines in collagen structure

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


glycines in collagen structure

-allow the chain to pack together


conversion of procollagen to tropocollagen is catalyzed by

-enzymes in the extracellular matrix


collagen and bone formation

-provides matrix for calcium phosphate deposition to make bones


osteogenesis imperfecta

-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


for have a function protein in many multi-domain proteins...
-this in relation to osteogenesis imperfecta

-all chains must be correct
-this is show in this disease because hets are severely effected


ehlers danols syndrome

-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)


transmissible spongiform encephalopathies

-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)


how do good prions go bad

-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