IAS06

Question 1

fibrous v globular

Answer 1

fibrous: long & narrow w/ extended repetitive sequence, insoluble in water
globular: spherical shape, water-soluble
fibrous: structural
globular: functional e.g. enzymes, transport, signalling

Question 2

collagen shape

Answer 2

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
-> high tensile strength

Question 3

collagen abundance

Answer 3

most abundant protein, keeps structure of skin, teeth, cartilage, bones

Question 4

proline hydroxylation

Answer 4

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

Question 5

clinical diseases of collagen

Answer 5

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, malaise, teeth loosening, anemia, swollen joint

Question 6

keratin structure

Answer 6

2x rh alpha helices twist into lh coiled-coil superhelical twist (dimeric)

Question 7

keratin abundance

Answer 7

in hair, skin, nails
but fungi pathogens feed on keratin

Question 8

keratin toughness

Answer 8

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

Question 9

red blood cell

Answer 9

lose organelles & nucleus, main function to carry O2 (98& protein is haemoglobin)

Question 10

haem group characteristics

Answer 10

prosthetic group, planar molecule w/ polphyrin ring, central Fe2+ binding to O2 for carrying 1x O2
both Fe & O2 stabilized by histidine

Question 11

myoglobin v haemoglobin

Answer 11

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

Question 12

ligand (OPTIONAL CARD)

Answer 12

atom/molecule binding to central metal atom to form coordination complex

Question 13

positive cooperativity

Answer 13

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

Question 14

positive cooperativity in haemoglobin

Answer 14

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

Question 15

positive cooperativity effect

Answer 15

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

Question 16

CO

Answer 16

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

Question 17

CO poisoning v anaemia

Answer 17

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

Question 18

protein folding

Answer 18

stepwise process w/ progressive stabilization of intermediates by creating short alpha helices
requires ATP to push/pull proteins to right conf.

Question 19

chaperones

Answer 19

assist folding or unfolding e.g. GroEL, GroES, HSP in humans (HSP useful for stress response & disease mechas)

Question 20

protein multiple folding

Answer 20

some w/ same AA sequence can exist and function diff. in multiple stable confs, e.g. lymphotactin (chemokine or binding glycosaminoglycan)

Question 21

protein folding diseases

Answer 21

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)

Question 22

alzheimer’s disease

Answer 22

improperly folded amyloid-beta protein self-associate into long fibrils -> aggregation into very long amyloid plaques -> toxicity