Collagen Flashcards
What are some characteristics of collagen?
Family of fibrous proteins found in all multicellular organisms.
28 types in humans, coded by 42 genes
Major proteins in bone, tendon and skin and the most abundant protein at 25% protein mass
How does the alignment of collagen fibres change from skin to mature bone and cornea?
Skin - layers at right angles to each other
Bone/cornea -same arrangement
Each collagen molecule comprises of three (a) chains forming a (b)
can be composed of one or more (a) chains such as (c) and (d)
a - alpha
b - triple helix
c - homotrymer
d - heterotymer
What is the composition of Type I collagen?
Chains from 2 different genes:
[ alpha 1 (I)] 2 and
[alpha 2 (I)]
What is the composition of Type II and Type III collagen respectively?
Both only have one chain type.
[alpha 1 (II)]3
[alpha 1 (III)]3
What is the characteristic collagen triple helix structure?
Three alpha chains form it.
Glycine, proline, hydroxyproline repeat
(glycine is small so occupies the interior of the helix - H side chain)
How are Collagen fibres assembles, smallest unit to largest?
One alpha chain
Three alpha chains
Collagen fibril (10-200nm)
Collagen fibre (0.5-3um)
(check histology for transverse and cross section)
What is procollagen?
Collagen with non-collagenous areas at N and C termini. (left and right ends)
these are removed after secretion for fibrillar collagens but remain for others
What gives collagen fibrils their tensile strength?
covalent crosslinks using lysine and hyodroxy lysine. between collagen helixes.
The regularity and extent of crosslinks changes with age
Why does Vitamin C deficiency compromise tissue stability?
VC and Fe2+ needed for prolyl and lysis hydroxylases.
Lysine and proline hydroxylation contributes to interchain hydrogen bond formation fformation
What post translational modification happens for lysine and hyroxylysine?
Modified in formation of covalent crosslinkages once collagen has been secreted.
Where is Collagen made?
mainly in the fibroblast cells
Once procollagens; the growing peptide chains are co-translationally transported into the lumen of the rough endoplasmic reticulum (ER).
What are Ehlers- Danlos syndromes?
EDS are inherited connective tissue disorders. stretchy skin and loose joints
mutations in collagen usually, affect production, structure or processing
e.g. brittle bone
What are some Fibril associated collagens?
IX and XII. will form fibrils and regulate the organisation of collagen fibrils
Collagen type IV is non-fibrillar, describe its assembly?
Collagen monomer forms a dimer, self assembles into tetramer and soon creates a supramolecular aggregate. Used in basement membranes
it is a network - forming collagen ! present in all basement membranes, though its arrangement moleculary can vary
What are Fibronectins?
What is their structural makeup?
Multi-adhesive Gylcoproteins in matrix and body fluids. Can be insoluble fibrillar matrix or soluble plasma proteins
Large multidomain molecule linked together by disulphide bonds. 500kD dimer is the basic unit
How are different fibronectins formed if they are derived from a single gene?
Alternate splicing of mRNAs giving rise to different types
What roles do Fibronectins play? (4)
Regulating cell adhesion (binds ligands e.g. collagen to integrin) and migration in variety of processes (embryogenesis and tissue repair)
Wound healing and blood clot promoting
What do Integrin receptors do?
At cell surface provide linkage between matrix and cell cytoskeleton
What are Proteoglycans?
The core proteins with covalently attached one or more GAG chains
Can be grouped as:
Basement membrane proteoglycans (perlecan)
Aggregating Proteoglycans (aggrecan)
Leucine rich proteoglycans (Decorin)
Cell surface proteoglycans (syndecans)
What are GAG chains
How do they contribute to the water in the ECM
Glycosaminoglycan chains
repeating disaccharide units with one sugar an amino sugar. Sulphated or carboxylated so have a high negative charge.
negative charge attracts cations including Na+ resulting in water being sucked into matrix
Cartilage has large amounts of GAGs trapped in matrix, so why are collagen fibres needed?
GAGS cause swelling pressure. This is negated by the tension in collagen fibres creating tensile strength
How are GAG chains grouped?
based on repeating disaccharide unit:
Hyaluronan
Chondroitin sulphate and dermatan sulphate
Heparan sulphate
Keratan sulphate
How is Hyaluronan GAG chains created compared to other GAGs chains
Spun out directly from enzyme embedded in plasma membrane
Others are synthesised and attached to core proteins in Endoplasmic Reticulum and Golgi Apparatus in cells
Why is Hyaluronan /Hyaluronic acid distinct from other GAGs?
Found in ECM in soft connective tissues. (vitreous humour of eye, synovial joint fluids)
Simply a carb chain without a core protein. Unsulphated.
Can undergo very high amounts of polymerisation, so occupy larger volumes. - up to 25,000 sugars, 10,000 disacharrides - take up a large volume
What are the characteristics of Aggrecan?
Cartilage ECM
Highly sulphated GAGs, increasing negative charge and lots of negative carboxyl groups
Large amounts of water in the environment which can resist compressive forces
What is the link between ECM and Osteoarthritis?
ECM degradation
With age, aggrecan is cleaved by aggrecanases and metalloproteinases.
Loss of aggrecan to synovial fluid
What are Fibrotic diseases due do?
Excessive production of fibrous connective tissue
E.g. Alcoholic liver cirrhosis
Fribrotic lung
Extra info
- in fibrillar collagens each ? chain is approximately 1000 amino acids, forming a left handed helix
basement membrane ? surround muscle, peripheral nerve and fat cells, underlie most epithelia. e.g. kidney glomerulus 300nm
- diabetic nephropathy : accumulation of ECM thick membrane - renal failure restricting filtration
