Amos, S-BTA, Kalli, AC orcid.org/0000-0001-7156-9403, Shi, J et al. (1 more author) (2019) Membrane Recognition and Binding by the Phosphatidylinositol Phosphate Kinase PIP5K1A: A Multiscale Simulation Study. Structure, 27 (8). 1336-1346.e2. ISSN 0969-2126
Abstract
Phosphatidylinositol phosphates (PIPs) are lipid signaling molecules that play key roles in many cellular processes. PIP5K1A kinase catalyzes phosphorylation of PI4P to form PIP2, which in turn interacts with membrane and membrane-associated proteins. We explore the mechanism of membrane binding by the PIP5K1A kinase using a multiscale molecular dynamics approach. Coarse-grained simulations show binding of monomeric PIP5K1A to a model cell membrane containing PI4P. PIP5K1A did not bind to zwitterionic or anionic membranes lacking PIP molecules. Initial encounter of kinase and bilayer was followed by reorientation to enable productive binding to the PI4P-containing membrane. The simulations suggest that unstructured regions may be important for the preferred orientation for membrane binding. Atomistic simulations indicated that the dimeric kinase could not bind to the membrane via both active sites at the same time, suggesting a conformational change in the protein and/or bilayer distortion may be needed for dual-site binding to occur.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2019 The Authors. Published by Elsevier Ltd. This is an open access article under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) |
Keywords: | lipid kinase; MD simulations; membranes; phosphatidylinositol phosphate |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 May 2019 12:35 |
Last Modified: | 25 Jun 2023 21:48 |
Status: | Published |
Publisher: | Elsevier (Cell Press) |
Identification Number: | 10.1016/j.str.2019.05.004 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:145672 |