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Membrane Chemistry Tunes the Structure of a Peptide Transporter
Author(s) -
LasitzaMale Tanya,
Bartels Kim,
Jungwirth Jakub,
Wiggers Felix,
Rosenblum Gabriel,
Hofmann Hagen,
Löw Christian
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202008226
Subject(s) - chemistry , lipid bilayer , membrane , cytoplasm , cooperativity , biophysics , membrane protein , bilayer , förster resonance energy transfer , biological membrane , protein–lipid interaction , peptide , transporter , membrane transport protein , biochemistry , fluorescence , gene , biology , physics , quantum mechanics
Abstract 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.