Structures and transport dynamics of a Campylobacter jejuni multidrug efflux pump

Su, Chih-Chia; Yin, Linxiang; Kumar, Nitin; Dai, Lei; Radhakrishnan, Abhijith; Bolla, Jani Reddy; Lei, Hsiang-Ting; Chou, Tsung-Han; Delmar, Jared A.; Rajashankar, Kanagalaghatta R.; Zhang, Qijing; Shin, Yeon-Kyun; Yu, Edward W.

doi:10.1038/s41467-017-00217-z

Structures and transport dynamics of a Campylobacter jejuni multidrug efflux pump

Journal Article · Tue Aug 01 04:00:00 EDT 2017 · Nature Communications

DOI:https://doi.org/10.1038/s41467-017-00217-z· OSTI ID:1377903

Su, Chih-Chia; Yin, Linxiang; Kumar, Nitin; Dai, Lei; Radhakrishnan, Abhijith; Bolla, Jani Reddy; Lei, Hsiang-Ting; Chou, Tsung-Han; Delmar, Jared A.; Rajashankar, Kanagalaghatta R.; Zhang, Qijing; Shin, Yeon-Kyun; Yu, Edward W. ^[1]

Cornell

Resistance-nodulation-cell division efflux pumps are integral membrane proteins that catalyze the export of substrates across cell membranes. Within the hydrophobe-amphiphile efflux subfamily, these resistance-nodulation-cell division proteins largely form trimeric efflux pumps. The drug efflux process has been proposed to entail a synchronized motion between subunits of the trimer to advance the transport cycle, leading to the extrusion of drug molecules. Here we use X-ray crystallography and single-molecule fluorescence resonance energy transfer imaging to elucidate the structures and functional dynamics of the Campylobacter jejuni CmeB multidrug efflux pump. We find that the CmeB trimer displays a very unique conformation. A direct observation of transport dynamics in individual CmeB trimers embedded in membrane vesicles indicates that each CmeB subunit undergoes conformational transitions uncoordinated and independent of each other. On the basis of our findings and analyses, we propose a model for transport mechanism where CmeB protomers function independently within the trimer.

Research Organization:: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)

Sponsoring Organization:: NIH

OSTI ID:: 1377903

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 8; ISSN 2041-1723

Publisher:: Nature Publishing Group

Country of Publication:: United States

Language:: ENGLISH

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