Fibrillar Proteins Flashcards
Fibrillar Proteins
insoluble protein that makes up the principal structural proteins of the body. High content of secondary structures that form rod-shaped microfibers (fibrils)
Abnormal Collagen cause dysfunction of ….
cardiovascular organs bone skin joints eyes
Amino acid composition of collagen
33% Gly, 10-13% Pro, 10% OH-Pro and 1% OH-Lys + other stuff
Enzymes needed to catalyze hydroxilation of Pro and Lys
Lyslyl hydroxylase
Prolyl-4-hydroxylase
Prolyl-3-hydroxylase
Hydroxilation enzymes require ….
Fe2+, O2, Vit C, and Alpha-ketoglutatrate
Collagen - primary composition, effects of primary composition
involve repeats of -Gly-Pro-Y and -Gly-X-Hyp
- Gly (smallest AA) : will fit into small places
- Pro : helix breaker : No Alpha Helix
- Cross links can be formed
Scurvy - cause, symptoms
Ascorbic acid deficiency (Vit C) - poor synthesis of collagen without Co-factor to support collagen enzymes, symptoms diverse
Polyproline type II helix
One strand of collagen
Loose, left-handed helix, with three residues per turn
Alpha helix
Right-hand coiled or spiral confirmation. Every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier
Secondary structure proteins - Hydrogen bonds hold together
Right handed triple helix
Right handed
Low bulkiness of Gly allows COLLAGEN to from
Collagen - secondary/tertiary sturtures
Polyprolive type II helix
Right handed triple helix (three member superhelix)
Fibrils
How to collagen for fibrils
they can aggregate in quater staggered parallel arrays and cross-link to form fibrils
Telopeptides
N and C terminal segmetns of the triple helical region
sites for crosslinking
lysyle amono oxidase
Convert Lys groups to ALLYSINE (an aldehyde)
COPPER dependent
collagen + elastin
Steps in Biosynth of Collagen
Ribosomes in RER 3 alpha chains translation Peptide chain a.k.a PRECOLLAGEN Lumen of RER Cleavage by signal peptidase PROCOLLAGEN Hydroxylation of lysine.proline by hydroxylysine residues Glycosylation begins Disulfide bond formation RER - Triple helical structure PROCOLLAGEN Shipped to GA Glycosylation complete Secretion by exocytosis (into ECM) Propeptides cleaved TROPOCOLLAGEN together form COLLAGEN FIBRILS together form COLLAGEN FIBERS Maturation (intra/inter crosslinks)
Collagenases - def, action
Matrix metalloprotienases (MMP's) that catalyze hydrolysis of collagens, which typically have long half lives Clips collagen, triple helix unwinds and further degrades by gelatinases
Collagen - types
Fibrillar : I-III, V, XI
Network Forming : IV
Fibirl associated : IX, XII
Ostegensis Imperfecta - def., types (severity)
genetic disorder of collagen type I (mutation in chain alpha 1 or alpha 2)
OI type 1 - mild and common (type IA and IB)
OI type II - most severe - death in utero
OI type III - progressively deforming - most severe past infancy
OI type IV - moderately severe - variety
Ehlers-Danlos Syndrome
Group of connective tissue disorders
Elastin - def., compostion, sturcture
Provides elasticity to tissues, fibrous, insoluble to water
Lacks regular secondary structure but contains an UNORDERED coiled structure
Composed of allysines (secondary)
Desmosine and Isodesmosine (tertiary)- covalently crosslink chains
Cytoskeleton - composed of
microtubles, intermediate filaments and microfilaments
Microfilament - composed of,
Actin
Myosin
Microtubles - composed of, affected by (action)
alpha and beta tubilin
Colchine - dissaemble microtubules
Taxol - inhibit microtuble formation through binding (cell cylce specific)
Vince Alkaloids - Inhibit microtubles formation
Taxanes and Epothilones - Enhance microtuble stability
Kinesin and Dyenins
K - move vesicles to the + end of microtubules
D - move vesicles to the - end of microtubules
