Shared Flashcard Set

Details

1013 Fibrous Proteins Dr Rosevear
UC MED 2015 1013 Fibrous Proteins Dr Rosevear
33
Medical
Graduate
10/13/2011

Additional Medical Flashcards

 


 

Cards

Term
Ehlers-Danlos Syndrome
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.
Term
Structural consequences of Arg134 to Cys mutation in Ehlers-Danlos syndrome?
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.
Term
Osteogenesis imperfecta
Definition
Family of mutations in structural collagen gene; usually involve mutation of Gly in the Gly-X-Y triplet to Ala, Val, Ser
Term
What are the 5 different levels of collagen structure?
Definition
primary sequence, minor helix, triple helix, tropocollagen, and fibril formation
Term
Collagen primary sequence facts
Definition
- Gly every third residue
- 15-30% Proline or hydroxyproline
- ~10% Alanine
- 1 to 5% hydroxylysine
Term
Collagen minor helix facts
Definition
- not an α-helix
- Type II or polyproline helix
- 3 residues/turn
Term
Collagen triple helix
Definition
- 3 type II helices (more extended than alpha-helix) wound around each other in a defined way forming a superhelix
Term
Tropocollagen and fibril formation levels of collagen structure
Definition
Tropocollagen - post-translational modification
Fibril Formation - self-assembly of collagen into fibrils
Term
Role of collagen in bone formation
Definition
40 nm gaps called “hole regions” in the collagen fibril serve as nucleation points for hydroxylapatite (Ca5(PO4)3OH) deposition and bone formation.
Term
Importance of tropocollagen H-bonding
Definition
inter-tropocollagen H-bonding stabilizes collagen fibril.
Term
Importance of 4-hydroxylproline residues
Definition
stereoelectronic effect fixes the proline pyrrolidine ring pucker in the triple helix, pre-organizing all 3 main-chain torsion angles
Term
how are the 3 type II helices in collagen stabilized?
Definition
by inter-strand hydrogen bonding
Term
roles of hydroxyproline in collagen
Definition
help stabilize the triple helix and stabilize the packing of tropocollagen into fibrils
Term
How is collagen originally synthesized? What do the prefixes mean?
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
Term
Steps in collagen biosynthesis
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.
Term
Functions of procollagen C-terminal propeptide
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
Term
Functions of procollagen N-terminal propeptides
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
Term
Where is cystine (formed from two cysteines) found in procollagen
Definition
Present only in N- and C-terminal propeptides
Term
role of disulfide bonds in C-terminal collagen propeptides
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
Term
role of disulfide bonds in N-terminal propeptides
Definition
Intra-chain disulfide bonds and non-helical regions are necessary for proper alignment of procollagen molecules in fibril
Term
Role hydroxylysine in collagen structure
Definition
necessary for attachment of carbohydrates (site for glycosylation) and necessary for secretion and stabilization of collagen
Term
Why is ascorbate essential?
Definition
ascorbate is required for correct action of lysine and proline hydroxylases, which form hydroxyproline and hydroxylysine
Term
Cross-links in mature collagen
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.
Term
How is lysine converted to allysine
Definition
Catalyzed by lysine oxidase, white fits in holes in collagen which are just large enough for the enzyme.
Term
Elastic cartilage
Definition
presence of elastin gives cartilage the ability to deform & spring back into shape (found in pinna of ear, walls of eustachian tube, epiglottis)
Term
Desmosine
Definition
unique cross-links made from 4 Lys residues that give elastin strong elastic properties
Term
Common aa's and secondary structure info on elastin
Definition
Mostly Gly, Ala and Val with some Lys. Has a coil structure, little other secondary structure
Term
How elastin differs from collagen
Definition
There is only one genetic type of elastin; no triple helix; no repeating structure; no hydroxylysine or carbohydrate; no extension peptides
Term
tropoelastin
Definition
soluble monomer of elastin, ~800 aa. Tropoelastin has no hydroxylysine or histidine residues
Term
Why does tropoelastin use a chaperone
Definition
to prevent large aggregate formation
Term
Main difference between open and closed states of elastin
Definition
They have different hydrogen-bond arrangements
Term
Thermodynamics behind elasticity of elastin
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.
Term
steps of Elastic fiber assembly
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
Supporting users have an ad free experience!