De Vecchis, D orcid.org/0000-0002-7732-5095, Reithmeier, RAF and Kalli, AC orcid.org/0000-0001-7156-9403 (2019) Molecular Simulations of Intact Anion Exchanger 1 Reveal Specific Domain and Lipid Interactions. Biophysical Journal, 117 (7). pp. 1364-1379. ISSN 0006-3495
Abstract
Anion exchanger 1 (AE1) is responsible for the exchange of bicarbonate and chloride across the erythrocyte plasma membrane. Human AE1 consists of a cytoplasmic and a membrane domain joined by a 33-residue flexible linker. Crystal structures of the individual domains have been determined, but the intact AE1 structure remains elusive. In this study, we use molecular dynamics simulations and modeling to build intact AE1 structures in a complex lipid bilayer that resembles the native erythrocyte plasma membrane. AE1 models were evaluated using available experimental data to provide an atomistic view of the interaction and dynamics of the cytoplasmic domain, the membrane domain, and the connecting linker in a complete model of AE1 in a lipid bilayer. Anionic lipids were found to interact strongly with AE1 at specific amino acid residues that are linked to diseases and blood group antigens. Cholesterol was found in the dimeric interface of AE1, suggesting that it may regulate subunit interactions and anion transport.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2019 Biophysical Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
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) |
Funding Information: | Funder Grant number Academy of Medical Sciences Not Known |
Depositing User: | Symplectic Publications |
Date Deposited: | 29 Aug 2019 08:51 |
Last Modified: | 21 Oct 2019 09:48 |
Status: | Published |
Publisher: | Biophysical Society |
Identification Number: | 10.1016/j.bpj.2019.08.029 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:150136 |