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Direct protein-lipid interactions shape the conformational landscape of secondary transporters

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Article number4151
JournalNature Communications
Early online date8 Oct 2018
Accepted/In press19 Sep 2018
E-pub ahead of print8 Oct 2018
PublishedOct 2018


King's Authors


Secondary transporters undergo structural rearrangements to catalyze substrate translocation across the cell membrane – yet how such conformational changes happen within a lipid environment remains poorly understood. Here, we combine hydrogen-deuterium exchange mass spectrometry (HDX-MS) with molecular dynamics (MD) simulations to understand how lipids regulate the conformational dynamics of secondary transporters at the molecular level. Using the homologous transporters XylE, LacY and GlpT from Escherichia coli as model systems, we discover that conserved networks of charged residues act as molecular switches that drive the conformational transition between different states. We reveal that these molecular switches are regulated by interactions with surrounding phospholipids and show that phosphatidylethanolamine interferes with the formation of the conserved networks and favors an inward-facing state. Overall, this work provides insights into the importance of lipids in shaping the conformational landscape of an important class of transporters.

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