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High Affinity Binding to Profilin by a Covalently Constrained, Soluble Mimic of Phosphatidylinositol-4,5-bisphosphate Micelles

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journal contribution
posted on 2009-09-18, 00:00 authored by Sarah M. Richer, Nichole K. Stewart, Sarah A. Webb, John W. Tomaszewski, Martha G. Oakley
Phosphoinositide (PI) lipids are essential regulators of a wide variety of cellular functions. We present here the preparation of a multivalent analogue of a phosphatidylinositol-4,5-bisphosphate (PIP2) micelle containing only the polar headgroup portion of this lipid. We show that this dendrimer binds to the cytoskeletal protein profilin with an affinity indistinguishable from that of PIP2, despite the fact that profilin discriminates between PIP2 and its monomeric hydrolysis product inositol-1,4,5-triphosphate (IP3) under physiological conditions. These data demonstrate that the diacylglycerol (DAG) moiety of PIP2 is not required for high-affinity binding and suggest that profilin uses multivalency as a key means to distinguish between the intact lipid and IP3. The class of soluble membrane analogues described here is likely to have broad applicability in the study of protein·PI interactions.