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

INTRODUCTION: LIPID-PROTEIN INTERACTIONS
group interacts differently with charged membrane proteins, and proteins often present
smaller affinities for PG than for PS and PA (Mall et al., 2002).
The complexity to the protein-charged lipid interaction problem is raised by the
position of amino acid residues in the protein surface. Basic helices with different
hydrophobic thickness were shown to present different selectivities to negatively
charged lipids. This was rationalized as the result of tilting of helices in the membrane,
that located basic residues away from the headgroup region where strong interactions
between proteins and lipid headgroups are more likely (Mall et al., 2002). Additionally,
experiments with model peptides showed that insertion of Tyr decreased binding
affinities to anionic phospholipids, suggesting that the presence of Tyr residues
prevented close association of anionic phospholipids and cationic residues (Mall et al.,
2000).
These results suggest that the effects of charge on the interactions between lipids
and membrane proteins, though important are not determinant, and will be strongly
dependent on the detailed structure of the peptide and its orientation in the membrane
(Mall et al., 2002). Binding affinities of proteins for lipids are generally presented
relative to the binding affinity of PC lipids. PC and PE lipids frequently present the
lowest affinities for membrane proteins.
Binding sites for hydrophobic molecules have been shown to exist for several
proteins distinct from the sites for interaction with annular lipids. These are called nonannular
sites. They are generally located between TM α-helices or at protein-protein
interfaces. For some cases, these sites are available for interaction with some lipids but
not for others (Lee, 2003). Some lipid molecules were shown in crystal structures of
proteins to be bound to such sites. These observations suggest that the binding affinities
for these sites are much higher than the ones observed for annular lipids (Lee et al.,
2003).
Notably, several protein domains bind specifically to one or more forms of
phosphorylated PIP molecules through interactions that are very specific. Such domains
are often found on proteins involved in signal transduction. Other proteins bind
specifically to some components of raft domains, establishing a mechanism for
targeting the protein to specific structures in the membrane (Epand, 2005; Pérez-Gil et
al., 2005).
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