Term
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Definition
| Heterogeneous group of connective tissue disorders. Symptoms include skin hyperextensibility and fragility, joint hypermobility, tissue fragility. Defects found in structural genes as well as enzymes involved in post-translational modifications (lysylhydroxylase, procollagen N-peptidase). Examples of structural gene mutations are Gly934 to Arg and Arg134 to Cys. |
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Term
| Structural consequences of Arg134 to Cys mutation in Ehlers-Danlos syndrome? |
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Definition
| The mutation is a substitution of Arg in the X position of the Gly-X-Y triplet. The Cys side-chain projects outside the triple helix enabling formation of an intermolecular disulfide bond with a Cys at position 134 from adjacent molecule, resulting in formation of molecular aggregates that cannot be efficiently secreted. |
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Term
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Definition
| Family of mutations in structural collagen gene; usually involve mutation of Gly in the Gly-X-Y triplet to Ala, Val, Ser |
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Term
| What are the 5 different levels of collagen structure? |
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Definition
| primary sequence, minor helix, triple helix, tropocollagen, and fibril formation |
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Term
| Collagen primary sequence facts |
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Definition
- Gly every third residue
- 15-30% Proline or hydroxyproline
- ~10% Alanine
- 1 to 5% hydroxylysine |
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Term
| Collagen minor helix facts |
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Definition
- not an α-helix
- Type II or polyproline helix
- 3 residues/turn |
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Term
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Definition
| - 3 type II helices (more extended than alpha-helix) wound around each other in a defined way forming a superhelix |
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Term
| Tropocollagen and fibril formation levels of collagen structure |
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Definition
Tropocollagen - post-translational modification
Fibril Formation - self-assembly of collagen into fibrils |
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Term
| Role of collagen in bone formation |
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Definition
| 40 nm gaps called “hole regions” in the collagen fibril serve as nucleation points for hydroxylapatite (Ca5(PO4)3OH) deposition and bone formation. |
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Term
| Importance of tropocollagen H-bonding |
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Definition
| inter-tropocollagen H-bonding stabilizes collagen fibril. |
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Term
| Importance of 4-hydroxylproline residues |
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Definition
| stereoelectronic effect fixes the proline pyrrolidine ring pucker in the triple helix, pre-organizing all 3 main-chain torsion angles |
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Term
| how are the 3 type II helices in collagen stabilized? |
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Definition
| by inter-strand hydrogen bonding |
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Term
| roles of hydroxyproline in collagen |
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Definition
| help stabilize the triple helix and stabilize the packing of tropocollagen into fibrils |
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Term
| How is collagen originally synthesized? What do the prefixes mean? |
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Definition
| preprocollagen. pre- is a signal sequence to insert into ER membrane. pro- are N- and C-terminal sequences that are cleaved after secretion, forming tropocollagen |
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Term
| Steps in collagen biosynthesis |
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Definition
Rough endoplasmic reticulum: synthesized as preprocollagen, insertion of procollagen into the lumen of the ER.
Lumen ER: hydroxylation of Pro & Lys, glycosylation of hydroxylysine.
Lumen of ER & Golgi: self-assembly, triple helix formation.
Secretory vesicle: procollagen prepared for secretion from cell, tropocollagen molecule secretion.
Extracellular: trimming of pro-peptides, self-assembly of collagen molecules into fibrils and then fibers. |
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Term
| Functions of procollagen C-terminal propeptide |
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Definition
| Are necessary for nucleation of triple helix formation and association of 3 polypeptide chains. Also have inter-strand disulfide bonds stabilize growing triple helix |
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Term
| Functions of procollagen N-terminal propeptides |
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Definition
Imp't for proper alignment of procollagen molecules in fibril,
feedback control of net collagen synthesis, and regulation of growth factor activity in extracellular matrix |
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Term
| Where is cystine (formed from two cysteines) found in procollagen |
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Definition
| Present only in N- and C-terminal propeptides |
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Term
| role of disulfide bonds in C-terminal collagen propeptides |
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Definition
| Inter-chain disulfide bonds are formed that aid in registered nucleation of triple-helix formation in a zipper-like fashion from the C-terminus to the N-terminus |
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Term
| role of disulfide bonds in N-terminal propeptides |
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Definition
| Intra-chain disulfide bonds and non-helical regions are necessary for proper alignment of procollagen molecules in fibril |
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Term
| Role hydroxylysine in collagen structure |
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Definition
| necessary for attachment of carbohydrates (site for glycosylation) and necessary for secretion and stabilization of collagen |
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Term
| Why is ascorbate essential? |
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Definition
| ascorbate is required for correct action of lysine and proline hydroxylases, which form hydroxyproline and hydroxylysine |
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Term
| Cross-links in mature collagen |
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Definition
| aldol cross-links formed between allysine-lysine, allysine-allysine, and lysine-histidine. There are no disulfide links. Cross-links occur mostly at N and C terminal regions. |
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Term
| How is lysine converted to allysine |
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Definition
| Catalyzed by lysine oxidase, white fits in holes in collagen which are just large enough for the enzyme. |
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Term
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Definition
| presence of elastin gives cartilage the ability to deform & spring back into shape (found in pinna of ear, walls of eustachian tube, epiglottis) |
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Term
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Definition
| unique cross-links made from 4 Lys residues that give elastin strong elastic properties |
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Term
| Common aa's and secondary structure info on elastin |
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Definition
| Mostly Gly, Ala and Val with some Lys. Has a coil structure, little other secondary structure |
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Term
| How elastin differs from collagen |
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Definition
| There is only one genetic type of elastin; no triple helix; no repeating structure; no hydroxylysine or carbohydrate; no extension peptides |
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Term
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Definition
| soluble monomer of elastin, ~800 aa. Tropoelastin has no hydroxylysine or histidine residues |
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Term
| Why does tropoelastin use a chaperone |
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Definition
| to prevent large aggregate formation |
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Term
| Main difference between open and closed states of elastin |
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Definition
| They have different hydrogen-bond arrangements |
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Term
| Thermodynamics behind elasticity of elastin |
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Definition
Stretching, due to a force, exposes the repeating hydrophobic regions to water.
When force removed, hydrophobic effect takes over and returns elastin to its original structure. Water is excluded, and entropy of the water increases. |
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Term
| steps of Elastic fiber assembly |
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Definition
1. Tropoelastin transported to plasma membrane where small aggregates are formed via cross-links
2. Aggregates increase in size
3. Aggregates transferred to extracellular microfibrils
4. Elastin aggregates on the microfibril coalesce into larger structures
5. Elastin aggregates further cross-linked to form elastic fiber |
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