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39 Cards in this Set
- Front
- Back
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What type of cells make collagen? where is it destined to function?
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Osteoblasts and fibroblasts - make collagen then secrete to ECM.
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Where in cells does collagen synthesis start?
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Nucleus - transcription of collagen a-helix DNA. N-term signal sequence tags the mRNA for transport to rough ER.
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What happens to ribosomes as they translate collagen mRNA into protein?
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The collagen protein N-terminus contains a Signal Sequence so they are translocated to the ER
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Why collagen mRNA goes to RER:
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Because the newly made protein has a signal sequence for it.
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What happens to Signal Sequence once protein gets to ER:
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Cleaved; yields collagen precursor that must be modified.
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2 types of post-translation modifications of pre-collagen propeptides:
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1. Hydrolxylation of selected prolines and lysines
2. Glycosylation of selected hydroxylysine residues. |
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What enzymes hydroxylate Prolines and Lysines?
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Prolyl hydroxylase
Lysyl hydroxylase |
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What do hydroxylation enzymes for collegen require?
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Fe2+, Ascorbate, and Oxygen
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What happens if Ascorbate is not available?
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Scurvy - Vit C is essential for keeping iron reduced, and if lacking collagen fibers cannot crosslink.
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Primary Polypeptide Sequence structure of Collagen:
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Gly-X-Y
-Y is typically Lysine or Proline |
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Secondary structure of Collagen:
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LH alpha-helix
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Quaternary structure of Collagen:
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RH superhelix
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What happens after post-translation modifications of Collagen a-helices?
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Assembly and Secretion
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How does the superhelix assemble?
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Starting with C-terminus ends, interchain disulfides form and allow the 3 helixes to zip up.
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Resulting structure of assembled procollagen
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-2 terminal end propeptides (nonhelical)
-Central superhelix (RH) |
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Where does Procollagen go after assembly:
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Secreted from ER to Golgi by vesicular transport; then vesicular transport to cell surface/Extracellular Matrix.
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Where are the propeptides of Procollagen cleaved?
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In the extracellular matrix.
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Enzymes that cleave propeptides from Procollagen:
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Procollagen peptidases
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What allows Collagen fibrils to form?
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Spontaneous association
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What allows Collagen Fibrils to Crosslink? (enzyme)
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Lysyl oxidase
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Products of Lysyl Oxidase:
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Allysine
Hydroxyallysine |
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What is Allysine?
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Lysine with its amino group replaced by an aldehyde
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How are the R-groups in the primary 2ndary helical structure of collagen oriented?
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Every third R-group (Glycine) projects toward helix interior.
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Requirements for Prolyl/Lysyl Hydroxylase:
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-Procollagen a-helix
-Ascorbate -Fe2+ -O2 -a-ketoglutarate |
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Type of reaction catalyzed by Prolyl/Lysyl hydrolyxase:
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Dioxygenase
-Oxidative decarboxylation of a-ketoglutarate -Hydroxylation of Pro/Lys |
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Purpose of hydroxylating proline:
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Increased stability of collagen
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Purpose of hydroxylating lysine:
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Ability to make interchain crosslinks
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Actually 2 reasons for hydroxylating lysine:
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1. Site for glycsolyation with Galactose and/or Glucose
2. Enables crosslinking |
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Difference between N-linked and O-linked glycosylation:
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Nlinked: specific residues Asn-x-Ser/Thr, ER, cotransltn.
Olinked: no sequence, Ser/Thr, Golgi, post-translation. |
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What type of glycosylation occurs on collagen?
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O-linked - in the golgi
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Rate limiting step in collagen assembly/synthesis:
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Cis-trans isomerization of proline - must occur before C-to-N zipperng up can occur.
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Type of crosslink that forms between 2 neighboring Allysines:
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Aldol condensation
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Type of crosslink that forms between an Allysine and Lysine:
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1. Schiff base
2. Amadori rearrangement link |
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3 types of collagen diseases:
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1. Inherited
2. Dietary 3. Autoimmune |
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2 Inherited collagen disorders:
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1. Osteogenesis imperfecta
2. Ehlers Danlos |
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Osteogenesis Imperfecta
-cause -inheritance -symptoms |
-mutation of gene for type I collagen
-auto dominant -brittle bones |
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Difference between OI type I vs. II:
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I = normal collagen, less
II = more severe; abnormal collagen |
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Dietary collagen disease/cause
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Scurvy - lack of ascorbate - unstable collagen.
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Autoimmune collagen disease:
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Bullous pemphigoid
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