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Evidence for phospholipid export from the bacterial inner membrane by the Mla ABC transport system

DOI: 10.1038/s41564-019-0481-y DOI Help

Authors: Gareth W. Hughes (University of Birmingham) , Stephen C. L. Hall (University of Birmingham) , Claire S. Laxton (University of Nottingham) , Pooja Sridhar (University of Birmingham) , Amirul H. Mahadi (University of Birmingham) , Caitlin Hatton (University of Warwick) , Thomas J. Piggot (Defence Science and Technology Laboratory; University of Southampton) , Peter J. Wotherspoon (University of Birmingham) , Aneika C. Leney (University of Birmingham) , Douglas G. Ward (University of Birmingham) , Mohammed Jamshad (University of Birmingham) , Vaclav Spana (University of Birmingham) , Ian T. Cadby (University of Birmingham) , Christopher Harding (University of Birmingham) , Georgia L. Isom (University of Birmingham) , Jack A. Bryant (University of Birmingham) , Rebecca J. Parr (University of Birmingham) , Yasin Yakub (University of Birmingham) , Mark Jeeves (University of Birmingham) , Damon Huber (University of Birmingham) , Ian R. Henderson (University of Queensland) , Luke A. Clifton (ISIS Pulsed Neutron and Muon Source) , Andrew L. Lovering (University of Birmingham) , Timothy J. Knowles (University of Birmingham)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Microbiology , VOL 106

State: Published (Approved)
Published: June 2019
Diamond Proposal Number(s): 14692

Abstract: The Mla pathway is believed to be involved in maintaining the asymmetrical Gram-negative outer membrane via retrograde phospholipid transport. The pathway is composed of three components: the outer membrane MlaA–OmpC/F complex, a soluble periplasmic protein, MlaC, and the inner membrane ATPase, MlaFEDB complex. Here, we solve the crystal structure of MlaC in its phospholipid-free closed apo conformation, revealing a pivoting β-sheet mechanism that functions to open and close the phospholipid-binding pocket. Using the apo form of MlaC, we provide evidence that the inner-membrane MlaFEDB machinery exports phospholipids to MlaC in the periplasm. Furthermore, we confirm that the phospholipid export process occurs through the MlaD component of the MlaFEDB complex and that this process is independent of ATP. Our data provide evidence of an apparatus for lipid export away from the inner membrane and suggest that the Mla pathway may have a role in anterograde phospholipid transport.

Journal Keywords: Biochemistry; Biological techniques; Enzyme mechanisms; Lipids; Pathogens

Subject Areas: Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography