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

INTRODUCTION: LIPID-PROTEIN INTERACTIONS
2.5. Anchoring of transmembrane domains
TM proteins are enriched in hydrophobic amino acids such as Leu, Ile, Val, Trp,
Tyr, and Phe. However, the occurrence of the aromatic amino acids Trp and Tyr are
strongly dependent on the position inside the TM segment. These aromatic amino acids
are particularly enriched at the end of TM sequences, close to the headgroup region of
the lipid bilayer (Wallin et al., 1997). Apparently, these aromatic residues exhibit strong
preferential interactions for the complex electrostatic carbonyl-glycerol environment of
the bilayer (see Fig. I.6). In this region the aromatic rings are stabilized, and,
simultaneously, penetration in the hydrocarbon core of the bilayer is somewhat
unfavourable due to exclusion of the flat aromatic rings (Yau et al., 1988, Braun and
von Heijne, 1999). Interestingly, another aromatic residue, Phe, does not exhibit
significant preferential localization in the membrane environment (Braun and von
Heijne, 1999).
Another important characteristic of TM domains is that they are generally flanked
by polar regions, rich in charged residues. Positively charged amino acids are found
close to the hydrophobic domain of the protein and in some cases they can even be
deeply inserted in this region (Caputo and London, 2003). The energetic cost of burying
of a charge in the hydrophobic environment of the lipid bilayer is very large, and in that
situation the long charged side chains of these residues protrude towards the headgroup
region in a phenomenon called “snorkling”. For acidic residues (Asp and Glu), the
absence of long side chains present a greater barrier for insertion in the hydrophobic
core of the bilayer. This is however observed for TM sequences with uninterrupted
hydrophobic domains of at least 12 residues (Caputo and London, 2004), and in these
conditions it was already proposed that the buried acidic residues can become
protonated (Monné et al., 1998).
2.6. Lipid-protein hydrophobic matching
Hydrophobic matching is not solely relevant for lipid-lipid interactions (Section
1.7), and the problem exists also for protein-lipid interactions. In this case, the
hydrophobic length of the TM domain of the protein should match to the hydrophobic
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