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
Intermediary filament - def., e.g.
Exclusively structural
Keratin (hard and soft)
Keratin - structure
Coiled coils - a dimer of alpha helices
OI type I
few to 100 fractures, no bone deformity, normal stature, , normal teeth, blue scelra
OI type II
Perinatal, lethal, dark blue sclera
OI type III
Severe, lots of bone deformity, short stature, bad teeth, blue sclera, frequent hearing loss
OI type IV
moderate to mild, some bone deformity, some hearing loss, some short stature, normal to gret sclera
Types of OI mutations - explanations
Null allele = nulceotide deletion of frameshift = incorrect mRNA = low alpha 1 collagen = OI type 1
Structural mutation - single nucleotide change for Gly = new AA = variying problems = OI type II, III, IV
