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Title: Profilin binding to sub-micellar concentrations of phosphatidylinositol (4,5) bisphosphate and phosphatidylinositol (3,4,5) trisphosphate
Contributor(s): Moens, P  (author)orcid ; Bagatolli, LA (author)
Publication Date: 2007
DOI: 10.1016/j.bbamem.2006.12.012
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Abstract: Profilin is a small (12–15 kDa) actin binding protein which promotes filament turnover. Profilin is also involved in the signaling pathwaylinking receptors in the cell membrane to the microfilament system within the cell. Profilin is thought to play critical roles in this signaling pathway through its interaction with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] (P.J. Lu, W.R. Shieh, S.G. Rhee, H.L. Yin, C.S. Chen, Lipid products of phosphoinositide 3-kinase bind human profilin with high affinity, Biochemistry 35 (1996) 14027–14034).To date, profilin's interaction with polyphosphoinositides (PPI) has only been studied in micelles or small vesicles. Profilin binds with high affinity to small clusters of PI(4,5)P2 molecules. In this work, we investigated the interactions of profilin with sub-micellar concentrations of PI(4,5)P2 and PI(3,4,5)P3. Fluorescence anisotropy was used to determine the relevant dissociation constants for binding of sub-micellar concentrations of fluorescently labeled PPI lipids to profilin and we show that these are significantly different from those determined for profilin interaction with micelles or small vesicles.We also show that profilin binds more tightly to sub-micellar concentrations of PI(3,4,5)P3 (KD=720 μM) than to sub-micellar concentrations of PI(4,5)P2 (KD=985 μM). Despite the low affinity for sub-micellar concentration of PI(4,5)P2, profilin was shown to bind to giant unilamellar vesicles in presence of 0.5% mole fraction of PI(4,5)P2. The implications of these findings are discussed.
Publication Type: Journal Article
Source of Publication: Biochimica et Biophysica Acta (BBA) - Biomembranes, 1768(3), p. 439-449
Publisher: Elsevier Science
Place of Publication: Amsterdam, Netherlands
ISSN: 0005-2736
Field of Research (FOR): 070308 Crop and Pasture Protection (Pests, Diseases and Weeds)
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
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