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

CLUSTERING OF PI(4,5)P 2 IN FLUID PC BILAYERS
are substrates of protein kinase C that bind strongly to PI(4,5)P (Laux et al., 2000;
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Wang et al., 2001). Although these proteins present saturated acyl-chains, this alone is
not expected to result in accumulation in rafts. It is possible that the proteins are crosslinked
via actin and this would increase significantly the preference for the cholesterol
enriched phase (McLaughlin et al., 2002). In model lipid membranes, the basic domain
of MARCKS responsible for binding to PI(4,5)P was able to sequester this
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phospholipid into clusters through electrostatic interactions (Denisov et al., 1998; Rauch
et al., 2002; Gambhir et al., 2004).
Recently, Redfern and Gericke (2004,2005) suggested an alternative method for
PI(4,5)P clustering. According to these authors, phosphatidylinositol lipids
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spontaneously clustered at and above physiological pH, and both in the gel and fluid
phases, when incorporated in zwitterionic bilayers. The mechanism proposed to achieve
non-uniform distribution of PI(4,5)P in the bilayer, was the establishment of hydrogen
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bonds between phosphatidylinositol headgroups, and no external agent (cholesterol or
proteins) was required. According to the authors, the same type of clustering behaviour
was observed for phosphatidylinositol monophosphates and polyphosphates. This latter
proposal is very controversial, as the presence of large charges in the headgroups of
phosphatidylinositol phosphates must result in strong repulsion between the molecules
(Pap et al., 1995), and consequently a clustering phenomena is expected to be unlikely.
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