IAS06 Flashcards
fibrous v globular protein
fibrous: long & narrow w/ extended repetitive sequence, insoluble in water
globular: spherical shape, water-soluble
fibrous: structural
globular: functional e.g. enzymes, transport, signalling
collagen shape
triple helix w/ glycine-proline-hydroxyproline recur
3 lh alpha helices wrap around to form rh superhelix -> self-assemble into supermolecular fibrils -> fibers
striations present due to regular interactions btn fibrils
collagen abundance
most abundant protein, keeps structure of skin, teeth, cartilage, bones
proline hydroxylation
sodium ascorbate (VC) keeps Fe2+ reduced -> cofactor for prolyl 4-hydroxylase activity -> hydroxylate proline to 4-hydroxyproline -> flip conformation from endo to exo
posttranslational modification
clinical diseases of collagen
osteogenesis imperfecta (OI): abnormally formed collagen due to mutations in type 1 collagen i.e. collagen defect
symptoms: increased bone fracture
scurvy: VC deficiency, no VC to keep Fe2+ reduced -> no hydroxyproline & collagen w/o structural integrity
symptoms: gum bleeds & disease, teeth loosening, anemia, weakness, swollen joint
keratin
in hair, nails, epithelium
but fungi pathogens feed on keratin
toughness maintained by disulfide bonds formed by cysteine -> more S-S bond, more tough
hair curling: make less tough by reduction -> curl -> make more tough by oxidation
red blood cell
lose organelles & nucleus, main function to carry O2 (98% of protein is haemoglobin)
haem group characteristics
prosthetic group, planar molecule w/ polphyrin ring, central Fe2+ binding to O2 for carrying 1x O2
both Fe & O2 stabilized by histidine
myoglobin v haemoglobin
both globin & O2 carriers (other e.g.: neuroglobin in neurons)
myoglobin: monomer, 1 haem, facilitates O2 diffusion in muscle, higher O2 affinity,
haemoglobin: tetramer, 4 haems, for O2 transport in blood, haem close to surface for binding accessibility, lower O2 affinity
positive cooperativity
binding of 1st ligand to 1st subunit -> stabilize protein in high-affinity conf. -> change conf. -> induce other subunits to change to same conf. by protein-protein interactions -> easier for next ligand(s) to bind to other subunit(s) i.e. w/ higher affinity
positive cooperativity in haemoglobin
in lung, binding of O2 to T-state Hb -> Hb shifts to R-state w/ higher affinity to O2 -> promote O2 binding w/ other sites -> affinity for O2 inc. -> other O2 more likely to bind to Hb
in tissue, O2 leaves Hb, Hb R->T state w/ lower affinity to O2 -> other O2 more likely to release from Hb
positive cooperativity effect
weak binding in low O2 conc., strong binding in high O2 conc. -> efficiency
enable O2 to saturate in Hb in lungs & release O2 to myoglobin in tissue
CO
released from poorly ventilated gas cookers / cooking in small spaces
binds to Hb more strongly than O2, displaces O2 from Hb, competitive inhibitor
locks Hb to R state -> disrupt cooperativity
CO poisoning v anaemia
CO poisoning more severe, cooperativity lost in CO poisoing -> Hb cannot release O2 to myoglobin in tissues when low O2 conc. (DOES NOT return to T state) -> no O2 supplied to tissues
i.e. binds to but DOES NOT release O2
protein folding & chaperones
stepwise process w/ progressive stabilization of intermediates e.g. by creating short alpha helices
requires ATP to push/pull proteins to right conf.
chaperones: proteins that assist folding or unfolding e.g. GroEL, GroES, HSP in humans (HSP useful for stress response & disease mechas)
