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

INTRODUCTION: LIPID-PROTEIN INTERACTIONS
In the presence of lipids with tendency to establish nonlamellar structures, cubic and
nonlamellar lipid phases can be formed in the interface with the protein as a response to
hydrophobic mismatch. Nonlamellar arrangements of lipids change the curvature of the
bilayer in the vicinity of the protein and allow for a better fitting of the hydrophobic
sections of both proteins and lipids (Killian, 2003).
Peptide backbone deformation, such as transition from α-helix to π-helix (helices
with a wider helical pitch), could be a possible mechanism for adjustment to situations
of hydrophobic mismatch. However, several studies have confirmed that the α-helical
structure is insensitive to hydrophobic mismatch and this strategy to minimize
hydrophobic mismatch is unlikely (de Planque and Killian, 2003). Nevertheless a recent
study suggests that TM α-helices may flex in the lipid bilayer in order to submerge most
of the hydrophobic domain inside the bilayer core (Yeagle et al., 2007).
The hydrophobic matching principle might be a mechanism by which the activity of
some membrane proteins can be modulated. Thickness variations induced either
internally or externally can trigger some proteins in or out of an active status. This has
already been observed for some ion pumps such as Ca 2+ -ATPase and Na + ,K + -ATPase
that exhibit maximum activity in bilayers with a specific number of carbon atoms (Lee,
2003).
2.7. Transmembrane protein-lipid interface
As already stated, the lipids on the vicinity of the protein can either stretch or
compress their acyl-chains in response to hydrophobic mismatch. In pure lipids this
often results in the observation of two different lipid populations in protein-lipid
systems. One of these is very similar to the lipid in the absence of the protein (but not
necessarily identical), and its contribution to the total lipid population is inversely
dependent on protein concentration. The other population is more significant at higher
protein/peptide concentrations, frequently presenting a different gel-fluid phase
transition temperature (smaller T m for bilayers thinner than the protein and higher T m for
thicker bilayers) as well as a smaller cooperativity for this transition (Liu et al., 2002;
Morein et al., 2002). These two components are expected to correspond to free and
protein-associated lipids, respectively.
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