Cofilin-Membrane Interactions: Electrostatic Effects in Phosphoinositide Lipid Binding.

Autor: Prakash S; CSIR - National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411008, India., Krishna A; CSIR - National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411008, India.; Current Address: School of Biological Sciences, University of Auckland, Auckland, 1010, New Zealand., Sengupta D; CSIR - National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411008, India.
Jazyk: angličtina
Zdroj: Chemphyschem : a European journal of chemical physics and physical chemistry [Chemphyschem] 2023 Feb 01; Vol. 24 (3), pp. e202200509. Date of Electronic Publication: 2022 Nov 04.
DOI: 10.1002/cphc.202200509
Abstrakt: The actin cytoskeleton interacts with the cell membrane primarily through the indirect interactions of actin-binding proteins such as cofilin-1. The molecular mechanisms underlying the specific interactions of cofilin-1 with membrane lipids are still unclear. Here, we performed coarse-grain molecular dynamics simulations of cofilin-1 with complex lipid bilayers to analyze the specificity of protein-lipid interactions. We observed the maximal interactions with phosphoinositide (PIP) lipids, especially PIP 2 and PIP 3 lipids. A good match was observed between the residues predicted to interact and previous experimental studies. The clustering of PIP lipids around the membrane bound protein leads to an overall lipid demixing and gives rise to persistent membrane curvature. Further, through a series of control simulations, we observe that both electrostatics and geometry are critical for specificity of lipid binding. Our current study is a step towards understanding the physico-chemical basis of cofilin-PIP lipid interactions.
(© 2022 Wiley-VCH GmbH.)
Databáze: MEDLINE
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