RT Journal Article
SR Electronic
T1 The conformational distribution of a major facilitator superfamily peptide transporter is modulated by the membrane composition
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.09.900316
DO 10.1101/2020.01.09.900316
A1 Tanya Lasitza Male
A1 Kim Bartels
A1 Felix Wiggers
A1 Gabriel Rosenblum
A1 Jakub Jungwirth
A1 Hagen Hofmann
A1 Christian Löw
YR 2020
UL http://biorxiv.org/content/early/2020/01/09/2020.01.09.900316.abstract
AB While structural biology aims at explaining the biological function of membrane proteins with their structure, it is unclear how these proteins are modulated by the complex lipid composition of membranes. Here, we address this question by mapping the conformational distribution of the bacterial oligopeptide transporter DtpA using single-molecule fluorescence spectroscopy. We show that DtpA populates ensembles of conformers that respond sensitively to the environment. Detergents trap the transporter in an inward-open ensemble in which the substrate binding site faces the cytosol. However, re-constitution in Saposin nanoparticles with different lipid compositions, reveal a plethora of alternative conformations, including a fully inward-open ensemble whose existence had not been anticipated before. The relative abundance of these ensembles depends on the lipid composition of the nanoparticles. Our results therefore demonstrate that membranes sensitively affect the structural distribution of DtpA and we expect this to be a general property of membrane proteins.