Naughton, FN, Kalli, AC orcid.org/0000-0001-7156-9403 and Sansom, MSP (2018) Modes of Interaction of Pleckstrin Homology Domains with Membranes: Toward a Computational Biochemistry of Membrane Recognition. Journal of Molecular Biology, 430 (3). pp. 372-388. ISSN 0022-2836
Abstract
Pleckstrin homology (PH) domains mediate protein–membrane interactions by binding to phosphatidylinositol phosphate (PIP) molecules. The structural and energetic basis of selective PH–PIP interactions is central to understanding many cellular processes, yet the molecular complexities of the PH–PIP interactions are largely unknown. Molecular dynamics simulations using a coarse-grained model enables estimation of free-energy landscapes for the interactions of 12 different PH domains with membranes containing PIP2 or PIP3, allowing us to obtain a detailed molecular energetic understanding of the complexities of the interactions of the PH domains with PIP molecules in membranes. Distinct binding modes, corresponding to different distributions of cationic residues on the PH domain, were observed, involving PIP interactions at either the “canonical” (C) and/or “alternate” (A) sites. PH domains can be grouped by the relative strength of their C- and A-site interactions, revealing that a higher affinity correlates with increased C-site interactions. These simulations demonstrate that simultaneous binding of multiple PIP molecules by PH domains contributes to high-affinity membrane interactions, informing our understanding of membrane recognition by PH domains in vivo.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Published by Elsevier Ltd. This is an author produced version of a paper published in Journal of Molecular Biology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | PH domains; Membrane; PIP; Molecular dynamics; Free-energy |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) |
Depositing User: | Symplectic Publications |
Date Deposited: | 18 Dec 2017 12:25 |
Last Modified: | 20 Dec 2018 01:38 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.jmb.2017.12.011 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:125266 |