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

Détails

Ressource 1Télécharger: sciadv.abm1122.pdf (1360.96 [Ko])
Etat: Public
Version: Author's accepted manuscript
Licence: CC BY-NC 4.0
ID Serval
serval:BIB_33FB9C761615
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Mechanistic basis of choline import involved in teichoic acids and lipopolysaccharide modification.
Périodique
Science advances
Auteur⸱e⸱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
Statut éditorial
Publié
Date de publication
04/03/2022
Peer-reviewed
Oui
Volume
8
Numéro
9
Pages
eabm1122
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
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
Oui
Création de la notice
07/03/2022 11:48
Dernière modification de la notice
27/08/2022 7:09
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