fibrous proteins Flashcards
what are examples of fibrous proteins
collagen, elastin and myosin
what are differences between globular and fibrous proteins
globular are compact, fibrous are extended
globular is water soluble
fibrous is insoluble in water and lipid bilayers
secondary structure of globular is more complex with a mixture of alpha helices, beta sheets and loops
fibrous secondary structure is based on one type only
globular quaternary structure is held together by noncovalent forces
fibrous quaternary structure is usually held together by covalent bonds
what are functions of fibrous proteins
bone, muscle, skin, hair etc
collagen in connective tissues relates to tensile strength
elastin in connective tissues relates to elasticity and stretchability
alpha keratin provides external protection and gives toughness to hair, nails and outer skin
what proportion of body protein is fibrous
half fibrous half globular
what are examples of mixed fibrous-globular protein
fibrinogen and myosin
what is the extracellular matrix
compex structural entity surrounding and supporting cells that are found within mammalian tissues, often referred to as connective tissue
composed of 3 major classes of biomolecules; structural proteins (collagen and elastin), specialised proteins (fibrillin and fibronectin) and proteoglycans
the extracellular matrix consists of fibrous proteins in a hydrated polysaccharide gel, connective tissue is this plus cells
what is structure of proteoglycans
protein core attached to long chains of repeating disaccharide units termed glycosaminoglycans (GAGs), forming extememly complex hgigh molecular weight components of the ECM
long carbohydrate chains which are highly negative charged (2 or 3 negative chargers per dimer)
what does the extracellular matrix effect
effects dynamic behaviour of cells by effecting; growth, migration, proliferation, shape and metabolism
what are cells found in the ECM
fibroblasts that secrete the matrix
chondroblasts which give rise to cartilage
oesteoblasts and oesteoclasts which are responsible for bone growth
these are all underlying an epithelial cell sheet
how many types of collages are there
over 20 types, type 1-3 are most abundant, they form fibrils of similar structure
describe the structure of a single collagen chain
2/3 of residues are proline (no alpha helices are formed, forms collagen helix instead)
every 3rd residue is glycine, one surface is relatively flat without bulk, this twists gently about the axis
produces a stable intertwined triple helix
substantial posttranslational processing of sidechains leads to strong cross links
describe the process of collagen assembly/ synthesis
synthesised as procollagen which is secreted from the cell
cleaved to tropocollagen by procollagen peptidase
assembly of tropocollagen leads to collagen fibre
chemical crosslinks of tropocollagen strengthens the fibre
describe the synthesis of procollagen
three seperate pro- a chains are synthesised in the cells
hydroxylation of selected proline and lysine residues occurs, uses proline and lysine hydroxylases which are dioxygenase enzymes
scurvey due to lack of vitamin C results in weakening of fibres at this stage
selected hydroxylated lysine residues are glycosylated
the pro-a chains assemble at the C terminus end starting with disulphide bridge formations between 3 chains, 3 chains then zip up to form procollagen
collagen is only protein to fold up prom C terminus onwards
describe basic structure of type 1 collagen
900 residues long, standard sequence is proline, hydroxy-proline, glycine which is repeated
how is tropocollagen formed
tropocollagen is formed by cleaving top and bottom loose strands to leave just the triple helix
N and C terminal peptides of procallagen are cleaved by procollagen peptidase
describe general structure of tropocollagen
tropocollagen is one of the most elongated proteins, length of 300nm
composition of tropocollagen; 35% glycine, 21% pro/hydroxy-pro, 12%ala and 32% other
secondary structure of tropocollagen is triple helix (not alpha helices or beta sheets)
describe features of tropocollagen secondary structure
features of triple helix;
3 seperate polypeptide chains arranged as a left handed helix, 3.3 residues per turn, each chains forms H bonds with other 2
there is a glycine every 3rd place, sidechains (H) point towards the centre of triple helix, leads to lots of H bonds, glycine is only source of H bonds between strands
glycine mainchain N-H protons form H bonds with C=O oxygen of adjacent polypeptide
pro and hy-pro are ‘imino’ acids and the side chain forms a covalent link with N atom so it cannot form H bonds, so glycine is buried in the middle while other 2 amino acids are on outside of triple helix
electron micrographs of a collagen fibre show cross striations with a repeat of about every 67nm, this is accounted for by the formation of one quater staggered array of tropocollagen molecules, since tropocollagen is 300nm long and 67nm is almost a quarter of that
how do tropocollagen molecules join with eachother
there are 40nm gaps between the tropocollagen molecules which is where calcium phosphate is deposited in bone formation
this assembly forms spontaneously by means of noncovalent H bond interactions involving the OH group of hydroxyproline
what causes scurvy, what are symptoms
a synthetic polymer made up of repeats of pro-pro-gly has a melting/ unfolding temp of 24 degrees (less than body temp)
if the second pro is replaced with hydroxy-pro this changes to 58 degrees, absence of this OH group leads to scurvy
symptoms are haemorrhages and blotchiness of skin, teeth fall out and people become lethargic
due to vitamin C (ascorbate) deficiency, so proline cannot be hydroxylated
how is tropocollagen converted to collagen
tropocollagen subunit assembly is strengthened by covalent crosslinks that are formed between lysine residues
lysyl oxidase generates a reactive aldehyde form of lysine which makes cross links
joining the CHO aldehyde group and the amino group of the other lysine residues leads to lysinonorleucine
if lysyl oxidase is hyperactive then both residues will be oxidised to aldehydes forming an adol link instead
after these covalent links are formed what is left is collagen
describe the alpha chains of collagen types 1-5
type 1: 2 alpha1 chains and 1 alpha2 chain
type 2 has 3 alpha1 chains
type 3 has 3 alpha 1 chains
type 4 has 2 alpha 1 and 1 alpha 2 chains
type 5 has 2 alpha 1 and 1 alpha 2
compare basic structure/function of collages types 1-6
type 4 collagen does not make a fibre
types 1-3 and 5-6 use fibronectin as an anchor, type 4 uses laminin
types that use fibronectin use cell surface receptor integrin, type 4 uses laminin receptors
describe structure of type 4 collagen, where is type 4 found
is a segmented molecule with kinks in it, monomers associate rapidly with head to head associations via C-terminal globular domains
dimers then form lateral associations via triple helical domains to form a sheet like meshwork
type 4 is present is epithelial cells, endothelial cells and regenerating hepatocytes, useful since epithelial and endothelial cells are flat
what is osteogenesis imperfecta
causes by a mutation in one or the other of 2 genes whose products are used to make type 1 collagen
all inherited collagen diseases, including this are dominant, since assembly of normal gene product with mutant gene product produces defective collagen fibres
common mutation is buried glycine residue to mutated cystine
clinical symptoms are brittle bones and skeletal deformaties
what is rubber man syndrome
caused by mutations in a type 1 collagen gene
symptoms are hyperextensible joints, tendons and skin
this is a type of ehlers danlos syndrome (type 7)
results from reduced levels of procollagen peptidase so not fully converted to tropocollagen
the 40nm gaps between tropocollagen molecules become blocked by uncleaved peptides which prevent lysyl oxidase from acting on tropocollagen to create the cross links
describe equation of hydroxylation of proline in procollagen
proline + oxygen + alphaketoglutarate - hydroxyproline + CO2 + succinate
what is lathyrism
an animal disease caused by ingestion of sweet pea seeds with beta aminopropionitrile or from copper deficiency
also occurs from low levels of lysyl oxidase (another form of ehlers danlos syndrome)
lysyl oxidase is a copper binding enzyme, beta aminopropionitrile prevents conversion of lys to aldehyde by irreversibly inhibiting lysyl oxidase
descibe structure of glycosaminoglycans
disaccharide repeating units, derivates of amino sugar, negatively charged (like proteoglycans)
GAGs are incorporated into proteoglycan aggregates
describe proteoglycan aggregates
form bottle brush structure:
a long chain of hyaluronic acid, link proteins are attached to long chain of hyaluronic acid, core protein of proteoglycans are attached to this, to the core proteins side chains of keratin sulphate and chondrotin sulphate split off
hyaluronic acid, keratin sulphate and chondrotin sulphate are glycosaminoglycans
when aqueous this has viscoelastic properties which helps support joints such as the knee
what forms cartilage
proteoglycans along with collagen
what is elastin, descibe primary structure
major component of elastic fibres in vasculature, found in major blood vessels and ligaments
the dominant sequence is pro-gly-val-gly-val-pro
a third of residues are gly
rich in pro and in small non polar residues
10% pro and hydroxy-pro, 23% ala, 13% val
descibe secondary structure of elastin
helical structure, not alpha helical or collagen triple helix though
it is able to stretch and relax like a coiled spring, it is called a beta spiral and is a helix constructed of beta turns
describe formation of elastin
synthesised as a proelastin, converted to tropoelastin (mol weight 72,000)
crosslinking of tropoelastin via lysine residues gives elastin crosslinks:
either desmosine (4 lysines) linking 2,3 or 4 molecules of tropoelastin
or lysinonorleucine (2 lysines)or adol link (2 lysines) linking 2 tropoelastin molecules
how is desmosine formed
4 lysines come together and are oxidised to an aldehyde and join together to form an aromatic ring, 3 are oxidised to an aldehyde, one remains as lysine
when lysine is converted to aldehyde the end CH2-NH2 group is converted into a CHO group
how is lysinonorleucine formed
one aldehyde reacts with lysine to form a “schiff base” where the end N of the lysine forms a double bond with the aldehyde forming a -N=CH- group
this is reduced to lysinonorleucine which has -N-CH2-
