Energetics of hydrophobic matching in lipid-protein interactions
Derek Marsh 1*
1 Max-Planck-Institut für biophysikalische Chemie
* To whom correspondence should be addressed. E-mail: dmarsh{at}gwdg.de.
Submitted on September 6, 2007
Revised on October 15, 2007
Accepted on 7 January 2008
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Abstract |
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Lipid chainlength modulates the activity of transmembrane proteins by mismatch between the hydrophobic span of the protein and that of the lipid membrane. Relative binding affinities of lipids with different chainlengths are used to estimate the excess free energy of lipid-protein interaction that arises from hydrophobic mismatch. For a wide range of integral proteins and peptides the energy cost is much less than the elastic penalty of fully stretching or compressing the lipid chains to achieve complete hydrophobic matching. The chainlength dependences of the free energies of lipid association are described by a model that combines elastic chain extension with a free energy term that depends linearly on the extent of residual mismatch. The excess free energy densities involved lie in the region of 0.52.0 kBT.nm-2. Values of this size could arise from exposure of hydrophobic groups to polar portions of the lipid or protein, but not directly to water, or alternatively from changes in tilt of the transmembrane helices that are energetically comparable to those activating mechanosensitive channels. The influence of hydrophobic mismatch on dimerisation of transmembrane helices and their transfer between lipid vesicles, and on shifts in chain-melting transitions of lipid bilayers by incorporated proteins, is analysed by using the same thermodynamic model. Segmental order parameters confirm that elastic lipid chain distortions are insufficient to compensate fully for the mismatch, but the dependence on chainlength with tryptophan-anchored peptides requires that the free energy density of hydrophobic mismatch should increase with increasing extent of mismatch.
Key Words:
chain order parameters, hydrophobic mismatch, intermembrane transfer, lipid binding, lipid chainlength, peptide dimerisation
