PW - Lipid Bilayer

Question 1

What is the influence of the bilayer on protein structure? (4)

Answer 1

• Proteins must interact with hydrophobic bilayer core
• Proteins must cope with change in environment at bilayer surface
• The bilayer is highly dynamic, but a solid interface is required between protein and bilayer to maintain bilayer integrity
• Must provide necessary architecture to carry out its function (signal transduction, transport)

Question 2

What is the most energetically favourable way to bury sequences in a hydrophobic environment? (2)

Answer 2

• Maximise entropy of the system
• Maximise enthalpy of the system

Question 3

What is involved in the energetics of inserting a peptide bond into a lipid bilayer?

Answer 3

Partial negative and positive charges on the peptide backbone have a high energetic cost

• Forming a hydrogen bond between beta sheets or helixes reduces the energetic cost

Question 4

What type of amino acids are less energetically favourable to be embedded in the membrane?

Answer 4

Charged amino acids or hydrophilic amino acids are less energetically favourable to be embedded in the membrane as they repel the hydrophobic core of the lipid bilayer

Question 5

What are 3 features of a-helical transmembrane domains?

Answer 5

• Each amino acid gives a rise of 1.5Å
• The bilayer thickness is ~36Å
• Require at least 24 residues to cross bilayer

Question 6

How do aromatic rings interact with environments?

Answer 6

Aromatic residues can exhibit both polar and apolar characteristics

• Allow protein to interact with charged environment in headgroup/aqueous phase and the hydrophobic core

Pi bonds are highly polarisable and so can interact with charged and hydrophobic regions

Question 7

What is the Positive inside rule?

Answer 7

Arg/Lys are typically found cytoplasmically

Question 8

What type of packing is typically preferred?

Answer 8

Helix interactions promoted by :

• Small sidechains : GXXXG
• Polar residues: SxxSSxxS

Stabilise the interaction between TMDs by increasing the surface contact

Question 9

b-Barrel Proteins : architecture (6)

Answer 9

• Anti-parallel b-sheet rolled into a barrel
• b-sheet is extended, only 7 residues needed to cross bilayer
• Typically strands are 9-11 residues long
• Strands typically slanted at 45°
• Stable structure (H-bonding contributes 10 amino acids per strand x 8 x 0.5 kcal/mol, 40 kcal/mole
• Size of pore determined by number of strands

Question 10

What is found in connections between strands? (2)

Answer 10

• Connections between extracellular loops tend to be long, and have high sequence variability
• Periplasmic loops are typically small formed by tight loops/turns

Question 11

What is the distribution of residues in b-barrels?

Answer 11

Internal surface

• Glycine present

External surface

• Tyrosine present as involved in interaction with solutes

Question 12

What are 2 features of extracellular loops?

Answer 12

• Loops cause constriction in pore
• Residues on loops can contribute to selectivity