Biophysical studies of membrane proteins/peptides. Interaction with ...

INTRODUCTION: LIPID-PROTEIN INTERACTIONS
excluded-volume interactions between headgroups. The resulting free-energy profile for
lipid-protein mismatch was nearly symmetrical about the point of hydrophobic
matching, and the lipid perturbation energy F (in units of kT per Å 2 of protein
circumference) is described by (Ben-Shaul, 1995):
F
( ) 2
= 0,37
+ 0,005 ⋅ d P
− d L
2.3
This model assumed concentration of the hydrophobic mismatch perturbation on the
first shell of lipids around the protein (see 2.7). For a hydrophobic mismatch of 7 Å and
assuming that each lipid adjacent to the protein should occupy at least 4 Å 2 of the
protein perimeter, the free-energy for lipid-protein interaction would increase by 3.6 kJ
mol -1 . This change in lipid-protein interaction energy corresponds to a decrease factor in
lipid-protein binding constant of 4.3. If propagation of perturbation spreaded to the
more external shells, the effects of hydrophobic mismatch on the adjacent lipid
molecules would be decreased. For example, if effects were averaged over three shells
of lipids, the change in binding constant would decrease by a factor of 1.6 (Mall et al.,
2002). Alternative models for treating hydrophobic mismatch came to very similar
conclusions regarding interaction energies (Nielsen et al., 1998; Mouritsen and Bloom,
1993).
Energies of this magnitude are sufficient to induce changes not only in the
interacting lipid molecules but in the protein itself. Experimental studies allowed to
conclude that β-barrel proteins are not easily susceptible to structural/conformational
changes due to hydrophobic mismatch and the energetic penalty for protein-lipid
interaction was only affecting lipid structure (O´Keeffe et al, 2000). However, in the
cases of alpha-helical TM proteins such as the potassium channel KcsA, and the
mechanosensitive channel MscL, the experimentally obtained dependence of binding
constants on the extent of hydrophobic mismatch was smaller than expected
(Williamson et al., 2002; Powl et al., 2003). This was rationalized as due to the smaller
rigidity of the α-helical proteins that makes them susceptible to distortion when
hydrophobic mismatch was present and therefore create an additional degree of freedom
for relaxation of lipid-protein hydrophobic mismatch. Distortion of α-helical membrane
proteins by hydrophobic mismatch is supported by the observation that the activities of
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