Biophysical studies of membrane proteins/peptides. Interaction with ...
Biophysical studies of membrane proteins/peptides. Interaction with ...
Biophysical studies of membrane proteins/peptides. Interaction with ...
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INTRODUCTION: LIPID-PROTEIN INTERACTIONS<br />
Partitioning <strong>of</strong> TM <strong>peptides</strong> to lipid bilayers is <strong>of</strong>ten a very difficult problem to<br />
study. A TM configuration for a peptide implies a large number <strong>of</strong> strongly<br />
hydrophobic residues in the sequence, as the size <strong>of</strong> the hydrophobic segment must be<br />
large enough to span the hydrocarbon (apolar) region <strong>of</strong> the bilayer (see Section 2.8). As<br />
a result their solubilities in water are frequently very low or null, and the partition<br />
equilibrium <strong>of</strong> these <strong>peptides</strong> is completely shifted to the lipid phase <strong>with</strong> almost no<br />
monomeric peptide in the aqueous environment (the available strategy to shield<br />
hydrophobic residues is non-specific aggregation). For these reasons the study <strong>of</strong><br />
lipid/water partition <strong>of</strong> TM <strong>peptides</strong> is frequently inaccessible apart from the<br />
considerations in Section 1.8. As for peripheral <strong>peptides</strong>, i.e. <strong>peptides</strong> that bind to the<br />
surface <strong>of</strong> lipid bilayers, the hydrophobicity requirements are not so severe and<br />
solubility in aqueous environments is <strong>of</strong>ten observed.<br />
The interaction <strong>of</strong> the peptide <strong>with</strong> the <strong>membrane</strong> is mainly dictated by the<br />
following effects:<br />
1) Electrostatic contributions are <strong>of</strong> key importance when basic residues are present in<br />
the peptide and the lipid surface is rich in negatively charged lipids. However, if the<br />
lipids are zwitterionic, the electrostatic influence can be negligible, and if both lipids<br />
and <strong>peptides</strong> present negative charges, the electrostatic contribution becomes negative<br />
(repulsion). In case <strong>of</strong> effective partition due to electrostatic attraction, this contribution<br />
is no longer independent <strong>of</strong> peptide concentration at very small lipid to peptide ratios<br />
(L/P). In this range <strong>of</strong> concentrations, the potential <strong>of</strong> the bilayer surface becomes<br />
dependent on the peptide concentration as a consequence <strong>of</strong> screening <strong>of</strong> lipid negative<br />
charges by the peptide (Seelig, 2004).<br />
2) Classical hydrophobic contributions are entropically driven, and result from the<br />
energetic requirements for insertion <strong>of</strong> apolar residues in the aqueous environment<br />
(rotational restriction <strong>of</strong> water molecules in the hydration shell). They are also<br />
dependent on the final positioning <strong>of</strong> the peptide in the lipid bilayer (bilayer surface or<br />
core).<br />
3) Perturbation <strong>of</strong> the lipid structure and packing.<br />
4) Hydrophobic matching <strong>of</strong> TM <strong>peptides</strong> (see Section 2.6).<br />
5) Hydrogen bonding properties <strong>of</strong> the lipid bilayer interface are highly complex, since<br />
both hydrogen bond donors and acceptors are present. As an example, PC bilayers<br />
establish stronger hydrogen bonds <strong>with</strong> phenolic compounds than PE bilayers due to the<br />
presence <strong>of</strong> the choline group. Additionally, the dielectric constant <strong>of</strong> the lipid bilayer<br />
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