How lipids affect the activities of integral membrane proteins

Lee, A.G. (2004) How lipids affect the activities of integral membrane proteins Biochimica et Biophysica Acta (BBA) - Biomembranes, 1666, (1-2), pp. 62-87. (doi:10.1016/j.bbamem.2004.05.012).


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The activities of integral membrane proteins are often affected by the structures of the lipid molecules that surround them in the membrane. One important parameter is the hydrophobic thickness of the lipid bilayer, defined by the lengths of the lipid fatty acyl chains. Membrane proteins are not rigid entities, and deform to ensure good hydrophobic matching to the surrounding lipid bilayer. The structure of the lipid headgroup region is likely to be important in defining the structures of those parts of a membrane protein that are located in the lipid headgroup region. A number of examples are given where the conformation of the headgroup-embedded region of a membrane protein changes during the reaction cycle of the protein; activities of such proteins might be expected to be particularly sensitive to lipid headgroup structure. Differences in hydrogen bonding potential and hydration between the headgroups of phosphatidycholines and phosphatidylethanolamines could be important factors in determining the effects of these lipids on protein activities, as well as any effects related to the tendency of the phosphatidylethanolamines to form a curved, hexagonal HII phase. Effects of lipid structure on protein aggregation and helix–helix interactions are also discussed, as well as the effects of charged lipids on ion concentrations close to the surface of the bilayer. Interpretations of lipid effects in terms of changes in protein volume, lipid free volume, and curvature frustration are also described. Finally, the role of non-annular, or ‘co-factor’ lipids, tightly bound to membrane proteins, is described.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1016/j.bbamem.2004.05.012
ISSNs: 0304-4165 (print)
Keywords: lipid–protein interaction, annular lipid, hydrophobic mismatch, membrane structure, membrane thickness lipid headgroup, non-annular lipid, integral membrane protein
ePrint ID: 56300
Date :
Date Event
3 November 2004Published
Date Deposited: 07 Aug 2008
Last Modified: 16 Apr 2017 17:41
Further Information:Google Scholar

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