Membrane lecture 8 Flashcards

1
Q

Signalling overview

A
  • Signal binds 7TM, GPCR binds G protein + activates → a+B subunits
  • 800 GPCRs
  • ↑ range of responses
  • Important drug target
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2
Q

Classification

A
  1. homology (Classes, classA = largest, rhodopsin-like, classC = metabotropic glutamate)
  2. Graf system
  3. Genetic structure (1st no = what helix residue of interest is on)
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3
Q

Rhodopsin

A
  • Found in rod cells
  • 2 glycosylation sites at NTD, N-2/15
  • 2 palmitoylation sites at C
  • Lys 296
  • Glycosylation on inside disc
  • Conversion of light (light causes retinal to isomerase, lys → trans, 1 rhodopsin activates 100 transducers, CGMP hydrolysed, allows Na+ to open,
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4
Q

Dynamics

A
  • Dynamic so ↑ conformational heterogeneity, hard to crystallise
  • Basal activity at low concentration of drug
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5
Q

Non-rhodopsin structure

A
  • B2 -adrenergic receptor

- Removed long flexible loop 3, lipid cubic phase

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6
Q

Key differences btw different states

A
  • Ionic lock (DRY/ERY at iC of TM3, salt bridge to E6/40 in inactive state)
  • Breaks upon activation
  • NPxxY on TM4
  • PIF motif
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7
Q

Activation

A
  • Lock opens, outward movement of TM5+6
  • Mutant E113Q, TM5/6 move away
  • Resting → intermediate state
  • Ionic lock x always broken
  • NPxxY conserved
  • Pif has subtle movement
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8
Q

Arrestin

A
  • Ligand induced conf change in GPCR facilitates interaction w/ G protein
  • GPCR = GEF for Ga
  • Second messengers = activated by effectors
  • B-arresting binds to phosph GPCR
  • Cells become desensitised
  • Agonist can bind and activate state that would be phosphorylated → arresting bound
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