Mechanistic basis of choline import involved in teichoic acids and lipopolysaccharide modification.

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State: Public
Version: Author's accepted manuscript
License: CC BY-NC 4.0
Serval ID
serval:BIB_33FB9C761615
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mechanistic basis of choline import involved in teichoic acids and lipopolysaccharide modification.
Journal
Science advances
Author(s)
Bärland N., Rueff A.S., Cebrero G., Hutter CAJ, Seeger M.A., Veening J.W., Perez C.
ISSN
2375-2548 (Electronic)
ISSN-L
2375-2548
Publication state
Published
Issued date
04/03/2022
Peer-reviewed
Oui
Volume
8
Number
9
Pages
eabm1122
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Phosphocholine molecules decorating bacterial cell wall teichoic acids and outer-membrane lipopolysaccharide have fundamental roles in adhesion to host cells, immune evasion, and persistence. Bacteria carrying the operon that performs phosphocholine decoration synthesize phosphocholine after uptake of the choline precursor by LicB, a conserved transporter among divergent species. Streptococcus pneumoniae is a prominent pathogen where phosphocholine decoration plays a fundamental role in virulence. Here, we present cryo-electron microscopy and crystal structures of S. pneumoniae LicB, revealing distinct conformational states and describing architectural and mechanistic elements essential to choline import. Together with in vitro and in vivo functional characterization, we found that LicB displays proton-coupled import activity and promiscuous selectivity involved in adaptation to choline deprivation conditions, and describe LicB inhibition by synthetic nanobodies (sybodies). Our results provide previously unknown insights into the molecular mechanism of a key transporter involved in bacterial pathogenesis and establish a basis for inhibition of the phosphocholine modification pathway across bacterial phyla.
Pubmed
Web of science
Open Access
Yes
Create date
07/03/2022 11:48
Last modification date
27/08/2022 7:09
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