The effects of lipids on channel function

Abstract

Anionic lipids affect the function of many channels, including connexins, as shown in a recent report in BMC Biology. These effects might follow from direct binding of the anionic lipids to the channels.

Figure 1

Lipid structures and phases. (a) The structure of the major glycerophospholipids phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol (PI), which differ only in the group indicated by X. Yellow indicates the hydrophobic tail; orange indicates the charged headgroup, which can be anionic or, where there is a positive and a negative charge, zwitterionic. (b) Lipids with a cylindrical shape, such as PC, pack as bilayers. (c) Lipids with a conical shape, such as PA or PE, pack in curved structures such as the hexagonal H_II phase.

Figure 2

Annular lipids. (a) Part of the transmembrane surface of aquaporin, showing bound annular lipid molecules. The protein is shown as a surface plot colored by charge (blue, positive; red, negative), with the lipid molecules shown in space-filling format (red, oxygen; orange, phosphorus; grey, carbon). From Protein DataBank (PDB) code 2B6O. (b) A snapshot from a molecular dynamics simulation of a transmembrane α-helix in a lipid bilayer. The helix is the sixth transmembrane α-helix of the potassium channel Kv. The lysine side chain can be seen hydrogen bonding to phosphate and ester oxygens of a phosphatidylcholine (PC) molecule, and the tryptophan side chain forms a hydrogen bond to an ester oxygen. Modified from [8].

Figure 3

How spontaneous curvature of lipids could affect channel function. The hydrophobic thickness of the lipid bilayer matches that of the channel in the closed state, but the hydrophobic thickness of the channel could increase on channel opening. This would require stretching of the lipid bilayer around the protein to maintain hydrophobic matching, and the associated curving of the bilayer would be easier if the lipid bilayer contains lipids that prefer to adopt a curved structure.