Insights into the bilayer-mediated toppling mechanism of a folate-specific ECF transporter by cryo-EM

Chancievan Thangaratnarajah, Jan Rheinberger, Cristina Paulino*, Dirk J Slotboom*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Energy-coupling factor (ECF)-type transporters are small, asymmetric membrane protein complexes (∼115 kDa) that consist of a membrane-embedded, substrate-binding protein (S component) and a tripartite ATP-hydrolyzing module (ECF module). They import micronutrients into bacterial cells and have been proposed to use a highly unusual transport mechanism, in which the substrate is dragged across the membrane by a toppling motion of the S component. However, it remains unclear how the lipid bilayer could accommodate such a movement. Here, we used cryogenic electron microscopy at 200 kV to determine structures of a folate-specific ECF transporter in lipid nanodiscs and detergent micelles at 2.7- and 3.4-Å resolution, respectively. The structures reveal an irregularly shaped bilayer environment around the membrane-embedded complex and suggest that toppling of the S component is facilitated by protein-induced membrane deformations. In this way, structural remodeling of the lipid bilayer environment is exploited to guide the transport process.

Original languageEnglish
Article numbere2105014118
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number34
Publication statusPublished - 24-Aug-2021

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