Membrane lecture 9

Question 1

Lipid composition

Answer 1

• Cholesterol + anionic lipids = important
• PIP2 has phospholipid, inositol groups + 2 P
• Lipids vary in head groups + FA tails

Question 2

Lipid ion channel structure

Answer 2

• Anionic lipids influence function of KV channel
• Cryo- EM of GABA ↑ res → PIP2 bound
• ANT1 binds CDL
• Free E landscape and see how Δ w/ different lipids
• Kir
• Pip2 mechanism

Question 3

Cholesterol

Answer 3

• Many GPCRs bind cholesterol

Question 4

PIP2

Answer 4

• -vely charged lipids could aid in allosteric activation of GPCR receptors
• GPCR add to MD w/ PIP2, show where PIP2 likely to bind
• conserved bs in class A receptors
• GPCR bound w/ PIP2

Question 5

Signalling

Answer 5

• EGFR → EGF binds → 7M helix dimer → tyrosine kinase domai

- TK autophosph → Ras → P13K → PIP3→PIP2 → ds signalling

Question 6

PTEN protein

Answer 6

• 2 domains, phosphatase _ C2
• Both bind PIP
• Tumour suppressor

Question 7

Receptor tyrosine kinase

Answer 7

• TM = reconstitution experiment
• Glycolipids like GM3 inhibit EGFR activation, PIP2 promotes dimerisation + activation
• Mutations in basic region weaken int. w/ GM3
  Stimulate juxtamembrane in bilayer