Membrane lecture 1

Question 1

Overview/importance

Answer 1

• 20% genes, 50% drug targets
• <1% structures determined
• Many = a-helical or bacteria outer-membrane proteins like OmpA = B-sheet
• 25-30% of all genes
• Diseases

Question 2

Environment + topologies

Answer 2

• Single TM can oligomerise
• Membrane associated proteins
• Integral membrane proteins
• Environment is important
• 2/3 state folding model (2o structure means peptide can satisfy backbone H bond requirements)

Question 3

Tm helix insertion

Answer 3

• Hydrophobic core = 30A thick, 20aa
• Ribosome, translocon (TM segments shunted sideways, gate btw TM2+7, plug = TM2A)
• Hydrophobic residues can be inserted
• Prediction

Question 4

Principle of membrane structure

Answer 4

• Analyse known structure of membrane to derive statistical rules
• Idea of length

Question 5

Key residues at interface

Answer 5

• Trp/tyr in porin + ion channels, can form H bond

- lys ‘snorkelling’

Question 6

Lipids

Answer 6

• Phosphatidylcholine to complex like PIP2
• Varies btw membranes
• Need good match btw hydrophobic protein + surrounding lips
• 1st shell of lipid = restricted
• Bacteriorhodopsin has hole occupied by up to 6 lipids