Journal Article

FZJ-2021-03191

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Structure and lipid dynamics in the maintenance of lipid asymmetry inner membrane complex of A. baumannii

Mann, D.FZJ* ; Fan, J. ; Somboon, K. ; Farrell, D. P. ; Muenks, A. ; Tzokov, S. B. ; DiMaio, F. ; Khalid, S. ; Miller, S. I. ; Bergeron, J. R. C. (Corresponding author)

2021
Springer Nature London

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Please use a persistent id in citations: http://hdl.handle.net/2128/28654  doi:10.1038/s42003-021-02318-4

Abstract: Multi-resistant bacteria are a major threat in modern medicine. The gram-negative coccobacillus Acinetobacter baumannii currently leads the WHO list of pathogens in critical need for new therapeutic development. The maintenance of lipid asymmetry (MLA) protein complex is one of the core machineries that transport lipids from/to the outer membrane in gram-negative bacteria. It also contributes to broad-range antibiotic resistance in several pathogens, most prominently in A. baumannii. Nonetheless, the molecular details of its role in lipid transport has remained largely elusive. Here, we report the cryo-EM maps of the core MLA complex, MlaBDEF, from the pathogen A. baumannii, in the apo-, ATP- and ADP-bound states, revealing multiple lipid binding sites in the cytosolic and periplasmic side of the complex. Molecular dynamics simulations suggest their potential trajectory across the membrane. Collectively with the recently-reported structures of the E. coli orthologue, this data also allows us to propose a molecular mechanism of lipid transport by the MLA system.

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Contributing Institute(s):

1. Strukturbiologie (ER-C-3)

Research Program(s):

1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)
2. 5352 - Understanding the Functionality of Soft Matter and Biomolecular Systems (POF4-535) (POF4-535)

Appears in the scientific report 2021

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