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

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