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A Mass‐Spectrometry‐Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins

Membrane proteins engage in a variety of contacts with their surrounding lipids, but distinguishing between specifically bound lipids, and non‐specific, annular interactions is a challenging problem. Applying native mass spectrometry to three membrane protein complexes with different lipid‐binding p...

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Autores principales: Bolla, Jani Reddy, Corey, Robin A., Sahin, Cagla, Gault, Joseph, Hummer, Alissa, Hopper, Jonathan T. S., Lane, David P., Drew, David, Allison, Timothy M., Stansfeld, Phillip J., Robinson, Carol V., Landreh, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065234/
https://www.ncbi.nlm.nih.gov/pubmed/31886601
http://dx.doi.org/10.1002/anie.201914411
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author Bolla, Jani Reddy
Corey, Robin A.
Sahin, Cagla
Gault, Joseph
Hummer, Alissa
Hopper, Jonathan T. S.
Lane, David P.
Drew, David
Allison, Timothy M.
Stansfeld, Phillip J.
Robinson, Carol V.
Landreh, Michael
author_facet Bolla, Jani Reddy
Corey, Robin A.
Sahin, Cagla
Gault, Joseph
Hummer, Alissa
Hopper, Jonathan T. S.
Lane, David P.
Drew, David
Allison, Timothy M.
Stansfeld, Phillip J.
Robinson, Carol V.
Landreh, Michael
author_sort Bolla, Jani Reddy
collection PubMed
description Membrane proteins engage in a variety of contacts with their surrounding lipids, but distinguishing between specifically bound lipids, and non‐specific, annular interactions is a challenging problem. Applying native mass spectrometry to three membrane protein complexes with different lipid‐binding properties, we explore the ability of detergents to compete with lipids bound in different environments. We show that lipids in annular positions on the presenilin homologue protease are subject to constant exchange with detergent. By contrast, detergent‐resistant lipids bound at the dimer interface in the leucine transporter show decreased k(off) rates in molecular dynamics simulations. Turning to the lipid flippase MurJ, we find that addition of the natural substrate lipid‐II results in the formation of a 1:1 protein–lipid complex, where the lipid cannot be displaced by detergent from the highly protected active site. In summary, we distinguish annular from non‐annular lipids based on their exchange rates in solution.
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spelling pubmed-70652342020-03-16 A Mass‐Spectrometry‐Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins Bolla, Jani Reddy Corey, Robin A. Sahin, Cagla Gault, Joseph Hummer, Alissa Hopper, Jonathan T. S. Lane, David P. Drew, David Allison, Timothy M. Stansfeld, Phillip J. Robinson, Carol V. Landreh, Michael Angew Chem Int Ed Engl Communications Membrane proteins engage in a variety of contacts with their surrounding lipids, but distinguishing between specifically bound lipids, and non‐specific, annular interactions is a challenging problem. Applying native mass spectrometry to three membrane protein complexes with different lipid‐binding properties, we explore the ability of detergents to compete with lipids bound in different environments. We show that lipids in annular positions on the presenilin homologue protease are subject to constant exchange with detergent. By contrast, detergent‐resistant lipids bound at the dimer interface in the leucine transporter show decreased k(off) rates in molecular dynamics simulations. Turning to the lipid flippase MurJ, we find that addition of the natural substrate lipid‐II results in the formation of a 1:1 protein–lipid complex, where the lipid cannot be displaced by detergent from the highly protected active site. In summary, we distinguish annular from non‐annular lipids based on their exchange rates in solution. John Wiley and Sons Inc. 2020-01-29 2020-02-24 /pmc/articles/PMC7065234/ /pubmed/31886601 http://dx.doi.org/10.1002/anie.201914411 Text en © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Communications
Bolla, Jani Reddy
Corey, Robin A.
Sahin, Cagla
Gault, Joseph
Hummer, Alissa
Hopper, Jonathan T. S.
Lane, David P.
Drew, David
Allison, Timothy M.
Stansfeld, Phillip J.
Robinson, Carol V.
Landreh, Michael
A Mass‐Spectrometry‐Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins
title A Mass‐Spectrometry‐Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins
title_full A Mass‐Spectrometry‐Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins
title_fullStr A Mass‐Spectrometry‐Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins
title_full_unstemmed A Mass‐Spectrometry‐Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins
title_short A Mass‐Spectrometry‐Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins
title_sort mass‐spectrometry‐based approach to distinguish annular and specific lipid binding to membrane proteins
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065234/
https://www.ncbi.nlm.nih.gov/pubmed/31886601
http://dx.doi.org/10.1002/anie.201914411
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