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Phospholipid transporter shifts into reverse

Nature Structural & Molecular Biology volume 28, pages 8–10 (2021)Cite this article

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The multisubunit phospholipid transport system Mla has been under scrutiny to determine whether it functions as an exporter or an importer. Structural studies accompanied by the reconstitution of the entire Mla system into proteoliposomes now reveal that ATP binding and hydrolysis drive phospholipid import.

The maintenance of outer membrane lipid asymmetry (Mla) phospholipid transport system of Escherichia coli is an ATP-binding cassette (ABC) transporter that was initially proposed to extract phospholipids from the external leaflet of the outer membrane for delivery to the inner membrane (retrograde flow). This functional assignment was based on genetic screens showing that mutants of the Mla system aberrantly accumulate phospholipids at the cell surface. Subsequent biochemical studies of the inner membrane ABC transporter subunits revealed that the Mla system spontaneously moves phospholipids toward the outer membrane (anterograde flow), but the role of ATP binding and hydrolysis in this process was not apparent. The resulting debate as to whether the Mla system drives retrograde versus anterograde phospholipid transport has called for the reconstitution of the inner and outer membrane Mla components into proteoliposomes, as was achieved previously for the lipopolysaccharide (LPS) transport system1. In this issue of Nature Structural & Molecular Biology, Tang et al.2 report a high resolution cryo-EM structure of the Mla inner membrane ABC transporter complex. The authors also reconstitute the entire Mla system into inner and outer membrane proteoliposomes. They confirm the previously reported spontaneous anterograde flow of phospholipids but critically demonstrate that ATP binding and hydrolysis shifts the Mla system into reverse, consistent with most of the genetic observations that have been accounted for previously by retrograde phospholipid transport.

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Fig. 1: Cell envelope phospholipid homeostasis defects in E. coli.

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  1. Department of Biochemistry and Biomedical Sciences and the Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada

    Russell E. Bishop

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Bishop, R.E. Phospholipid transporter shifts into reverse. Nat Struct Mol Biol 28, 8–10 (2021). https://doi.org/10.1038/s41594-020-00546-6

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