New insights into bacterial protein trafficking

The Koronakis group has published a study that provides new insights into a protein trafficking system essential for the survival and pathogenicity of many bacteria.

The work has the potential to aid the development of new antibiotics. 

Present in all bacteria, lipoproteins are anchored in the membrane by lipid chains and perform a myriad of functions, maintaining the integrity of the cell envelope, capturing essential nutrients, or mediating infections. As a result, the Lol system, responsible for lipoprotein transport to the outer membrane, is essential for the viability of bacteria like E. coli and Salmonella and is a key target for the development of new antibiotics. Lipoproteins—transported by the system—vary tremendously in size and shape, yet all are carried to the outer membrane by the LolA protein.

Using a combination of structural, biochemical, and microbiological techniques, a study led by Drs Elise Kaplan and Nicholas Greene from the Koronakis lab reveals how the LolA chaperone opens to accommodate the three lipoprotein lipid chains inside a central cavity. No interactions with the protein residues occurred, explaining how the chaperone can transport such structurally diverse lipoproteins. The lipoprotein binding site overlaps with that for another protein, LolC, part of a protein complex that recruits LolA to enable loading, suggesting that insertion of the lipoprotein lipid chains into LolA promotes release from the inner membrane transporter LolCDE to facilitate onward trafficking.

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The new structure will aid efforts to design new antibiotics that target this essential system and is part of a broader effort by the Koronakis group to understand the function of bacterial transport systems. The work is supported by a programme grant from the Medical Research Council.

Kaplan E, Greene NP, Jepson A & Koronakis V (2022) Structural basis of lipoprotein recognition by the bacterial Lol trafficking chaperone LolA in Proceedings of the National Academy of Sciences can be accessed here: https://doi.org/10.1073/pnas.2208662119

Authors

elise_kaplan.jpg   Dr Elise Kaplan Research Associate	greene_nick_2_crop.jpg   Dr Nick Greene Research Associate
abigail_jepson1.jpg   Abigail Jepson PhD Student	koronakis_vassilis_2_crop.jpg   Professor Vassilis Koronakis Principal Investigator

Reference:

Kaplan E, Greene NP, Jepson A & Koronakis V (2022) Structural basis of lipoprotein recognition by the bacterial Lol trafficking chaperone LolA. Proceedings of the National Academy of Sciences 119 (36) e2208662119

https://doi.org/10.1073/pnas.2208662119