The architecture of the OmpC-MlaA complex sheds light on the maintenance of outer membrane lipid asymmetry in Escherichia coli.

The Journal of Biological Chemistry
Jiang YeowShu-Sin Chng

Abstract

A distinctive feature of the Gram-negative bacterial cell envelope is the asymmetric outer membrane (OM), where lipopolysaccharides and phospholipids (PLs) reside in the outer and inner leaflets, respectively. This unique lipid asymmetry renders the OM impermeable to external insults, including antibiotics and bile salts. In Escherichia coli, the complex comprising osmoporin OmpC and the OM lipoprotein MlaA is believed to maintain lipid asymmetry by removing mislocalized PLs from the outer leaflet of the OM. How this complex performs this function is unknown. Here, we defined the molecular architecture of the OmpC-MlaA complex to gain insights into its role in PL transport. Using in vivo photo-cross-linking and molecular dynamics simulations, we established that MlaA interacts extensively with OmpC and is located entirely within the lipid bilayer. In addition, MlaA forms a hydrophilic channel, likely enabling PL translocation across the OM. We further showed that flexibility in a hairpin loop adjacent to the channel is critical in modulating MlaA activity. Finally, we demonstrated that OmpC plays a functional role in maintaining OM lipid asymmetry together with MlaA. Our work offers glimpses into how the OmpC-MlaA complex trans...Continue Reading

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Citations

Aug 20, 2019·The Journal of Biological Chemistry·Rahul Shrivastava, Shu-Sin Chng
Aug 20, 2019·Proceedings of the National Academy of Sciences of the United States of America·Matthew J Powers, M Stephen Trent
Apr 8, 2020·Infection and Immunity·Nicole P GiordanoZachary D Dalebroux
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Mar 4, 2020·Computational and Structural Biotechnology Journal·Karolina MitusińskaArtur Góra
Sep 22, 2020·Chemical Reviews·Emily LundstedtNatividad Ruiz
Apr 13, 2021·Journal of Molecular Biology·Changping ZhouYihua Huang
Dec 8, 2021·Proceedings of the National Academy of Sciences of the United States of America·Wen-Yi LowShu-Sin Chng

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