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Membrane Chemistry Tunes the Structure of a Peptide Transporter

Membrane proteins require lipid bilayers for function. While lipid compositions reach enormous complexities, high‐resolution structures are usually obtained in artificial detergents. To understand whether and how lipids guide membrane protein function, we use single‐molecule FRET to probe the dynami...

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Detalles Bibliográficos
Autores principales: Lasitza‐Male, Tanya, Bartels, Kim, Jungwirth, Jakub, Wiggers, Felix, Rosenblum, Gabriel, Hofmann, Hagen, Löw, Christian
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/PMC7590137/
https://www.ncbi.nlm.nih.gov/pubmed/32744783
http://dx.doi.org/10.1002/anie.202008226
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author Lasitza‐Male, Tanya
Bartels, Kim
Jungwirth, Jakub
Wiggers, Felix
Rosenblum, Gabriel
Hofmann, Hagen
Löw, Christian
author_facet Lasitza‐Male, Tanya
Bartels, Kim
Jungwirth, Jakub
Wiggers, Felix
Rosenblum, Gabriel
Hofmann, Hagen
Löw, Christian
author_sort Lasitza‐Male, Tanya
collection PubMed
description Membrane proteins require lipid bilayers for function. While lipid compositions reach enormous complexities, high‐resolution structures are usually obtained in artificial detergents. To understand whether and how lipids guide membrane protein function, we use single‐molecule FRET to probe the dynamics of DtpA, a member of the proton‐coupled oligopeptide transporter (POT) family, in various lipid environments. We show that detergents trap DtpA in a dynamic ensemble with cytoplasmic opening. Only reconstitutions in more native environments restore cooperativity, allowing an opening to the extracellular side and a sampling of all relevant states. Bilayer compositions tune the abundance of these states. A novel state with an extreme cytoplasmic opening is accessible in bilayers with anionic head groups. Hence, chemical diversity of membranes translates into structural diversity, with the current POT structures only sampling a portion of the full structural space.
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spelling pubmed-75901372020-10-30 Membrane Chemistry Tunes the Structure of a Peptide Transporter Lasitza‐Male, Tanya Bartels, Kim Jungwirth, Jakub Wiggers, Felix Rosenblum, Gabriel Hofmann, Hagen Löw, Christian Angew Chem Int Ed Engl Research Articles Membrane proteins require lipid bilayers for function. While lipid compositions reach enormous complexities, high‐resolution structures are usually obtained in artificial detergents. To understand whether and how lipids guide membrane protein function, we use single‐molecule FRET to probe the dynamics of DtpA, a member of the proton‐coupled oligopeptide transporter (POT) family, in various lipid environments. We show that detergents trap DtpA in a dynamic ensemble with cytoplasmic opening. Only reconstitutions in more native environments restore cooperativity, allowing an opening to the extracellular side and a sampling of all relevant states. Bilayer compositions tune the abundance of these states. A novel state with an extreme cytoplasmic opening is accessible in bilayers with anionic head groups. Hence, chemical diversity of membranes translates into structural diversity, with the current POT structures only sampling a portion of the full structural space. John Wiley and Sons Inc. 2020-09-11 2020-10-19 /pmc/articles/PMC7590137/ /pubmed/32744783 http://dx.doi.org/10.1002/anie.202008226 Text en © 2020 The Authors. Published by Wiley-VCH GmbH 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 Research Articles
Lasitza‐Male, Tanya
Bartels, Kim
Jungwirth, Jakub
Wiggers, Felix
Rosenblum, Gabriel
Hofmann, Hagen
Löw, Christian
Membrane Chemistry Tunes the Structure of a Peptide Transporter
title Membrane Chemistry Tunes the Structure of a Peptide Transporter
title_full Membrane Chemistry Tunes the Structure of a Peptide Transporter
title_fullStr Membrane Chemistry Tunes the Structure of a Peptide Transporter
title_full_unstemmed Membrane Chemistry Tunes the Structure of a Peptide Transporter
title_short Membrane Chemistry Tunes the Structure of a Peptide Transporter
title_sort membrane chemistry tunes the structure of a peptide transporter
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590137/
https://www.ncbi.nlm.nih.gov/pubmed/32744783
http://dx.doi.org/10.1002/anie.202008226
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