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A lipid gating mechanism for the channel-forming O antigen ABC transporter

Abstract:
Extracellular glycan biosynthesis is a widespread microbial protection mechanism. In Gram-negative bacteria, the O antigen polysaccharide represents the variable region of outer membrane lipopolysaccharides. Fully assembled lipid-linked O antigens are translocated across the inner membrane by the WzmWzt ABC transporter for ligation to the lipopolysaccharide core, with the transporter forming a continuous transmembrane channel in a nucleotide-free state. Here, we report its structure in an ATP-bound conformation. Large structural changes within the nucleotide-binding and transmembrane regions push conserved hydrophobic residues at the substrate entry site towards the periplasm and provide a model for polysaccharide translocation. With ATP bound, the transporter forms a large transmembrane channel with openings toward the membrane and periplasm. The channel’s periplasmic exit is sealed by detergent molecules that block solvent permeation. Molecular dynamics simulation data suggest that, in a biological membrane, lipid molecules occupy this periplasmic exit and prevent water flux in the transporter’s resting state.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-019-08646-8

Authors


More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Biochemistry
Oxford college:
Christ Church
Role:
Author
ORCID:
0000-0001-6360-7959
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author
ORCID:
0000-0001-8800-7669


Publisher:
Springer Nature
Journal:
Nature Communications More from this journal
Volume:
10
Article number:
824
Publication date:
2019-02-18
Acceptance date:
2019-01-23
DOI:
EISSN:
2041-1723


Language:
English
Keywords:
Pubs id:
pubs:974328
UUID:
uuid:aad2e8c8-16f9-4f50-9b5f-55655ad4dca4
Local pid:
pubs:974328
Source identifiers:
974328
Deposit date:
2019-02-18

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