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Title: Allostery revealed within lipid binding events to membrane proteins

Abstract

Membrane proteins interact with a myriad of lipid species in the biological membrane, leading to a bewildering number of possible protein–lipid assemblies. Despite this inherent complexity, the identification of specific protein–lipid interactions and the crucial role of lipids in the folding, structure, and function of membrane proteins is emerging from an increasing number of reports. Fundamental questions remain, however, regarding the ability of specific lipid binding events to membrane proteins to alter remote binding sites for lipids of a different type, a property referred to as allostery. Here, we use native mass spectrometry to determine the allosteric nature of heterogeneous lipid binding events to membrane proteins. We monitored individual lipid binding events to the ammonia channel (AmtB) from Escherichia coli, enabling determination of their equilibrium binding constants. We found that different lipid pairs display a range of allosteric modulation. In particular, the binding of phosphatidylethanolamine and cardiolipin-like molecules to AmtB exhibited the largest degree of allosteric modulation, inspiring us to determine the cocrystal structure of AmtB in this lipid environment. The 2.45-Å resolution structure reveals a cardiolipin-like molecule bound to each subunit of the trimeric complex. Furthermore, mutation of a single residue in AmtB abolishes the positive allosteric modulation observedmore » for binding phosphatidylethanolamine and cardiolipin-like molecules. Our results demonstrate that specific lipid–protein interactions can act as allosteric modulators for the binding of different lipid types to integral membrane proteins.« less

Authors:
 [1];  [1];  [2];  [1];  [2];  [2];  [1]
+ Show Author Affiliations
  1. Texas A & M Univ., College Station, TX (United States)
  2. Texas A&M Health Science Center, Houston, TX (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH), National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH), Office of Research Infrastructure Programs High-End Instrumentation Grant
OSTI Identifier:
1433699
Grant/Contract Number:  
AC02-06CH11357; DP2GM123486; P41 GM103403; S10OD021527
Resource Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 115; Journal Issue: 12; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; native mass spectrometry; lipids; membrane proteins; lipid−protein interactions; allostery

Citation Formats

Patrick, John W., Boone, Christopher D., Liu, Wen, Conover, Gloria M., Liu, Yang, Cong, Xiao, and Laganowsky, Arthur. Allostery revealed within lipid binding events to membrane proteins. United States: N. p., 2018. Web. doi:10.1073/pnas.1719813115.
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Patrick, John W., Boone, Christopher D., Liu, Wen, Conover, Gloria M., Liu, Yang, Cong, Xiao, & Laganowsky, Arthur. Allostery revealed within lipid binding events to membrane proteins. United States. https://doi.org/10.1073/pnas.1719813115
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Patrick, John W., Boone, Christopher D., Liu, Wen, Conover, Gloria M., Liu, Yang, Cong, Xiao, and Laganowsky, Arthur. Mon . "Allostery revealed within lipid binding events to membrane proteins". United States. https://doi.org/10.1073/pnas.1719813115. https://www.osti.gov/servlets/purl/1433699.
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@article{osti_1433699,
title = {Allostery revealed within lipid binding events to membrane proteins},
author = {Patrick, John W. and Boone, Christopher D. and Liu, Wen and Conover, Gloria M. and Liu, Yang and Cong, Xiao and Laganowsky, Arthur},
abstractNote = {Membrane proteins interact with a myriad of lipid species in the biological membrane, leading to a bewildering number of possible protein–lipid assemblies. Despite this inherent complexity, the identification of specific protein–lipid interactions and the crucial role of lipids in the folding, structure, and function of membrane proteins is emerging from an increasing number of reports. Fundamental questions remain, however, regarding the ability of specific lipid binding events to membrane proteins to alter remote binding sites for lipids of a different type, a property referred to as allostery. Here, we use native mass spectrometry to determine the allosteric nature of heterogeneous lipid binding events to membrane proteins. We monitored individual lipid binding events to the ammonia channel (AmtB) from Escherichia coli, enabling determination of their equilibrium binding constants. We found that different lipid pairs display a range of allosteric modulation. In particular, the binding of phosphatidylethanolamine and cardiolipin-like molecules to AmtB exhibited the largest degree of allosteric modulation, inspiring us to determine the cocrystal structure of AmtB in this lipid environment. The 2.45-Å resolution structure reveals a cardiolipin-like molecule bound to each subunit of the trimeric complex. Furthermore, mutation of a single residue in AmtB abolishes the positive allosteric modulation observed for binding phosphatidylethanolamine and cardiolipin-like molecules. Our results demonstrate that specific lipid–protein interactions can act as allosteric modulators for the binding of different lipid types to integral membrane proteins.},
doi = {10.1073/pnas.1719813115},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 12,
volume = 115,
place = {United States},
year = {Mon Mar 05 00:00:00 EST 2018},
month = {Mon Mar 05 00:00:00 EST 2018}
}
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https://doi.org/10.1073/pnas.1719813115
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