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 loss
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)
protein multiple folding
some w/ same AA sequence can exist and function diff. in multiple stable confs
protein folding diseases
amyloid disease: abnormal protein (amyloid fibril) buildup in tissues in organs caused by protein misfolding e.g. diabetes mellitus II (islet amyloid PP), huntington’s (huntingtin), atherosclerosis (APOA1), systematic amyloidosis (light chain antibody amyloid), alzheimer’s (amyloid beta protein), prion diseases (PrPSC)
alzheimer’s disease
improperly folded amyloid-beta protein self-associate into long fibrils -> aggregation into very long amyloid plaques -> toxicity
