Bärland, Natalie and Rueff, Anne-Stéphanie and Cebrero, Gonzalo and Hutter, Cedric A. J. and Seeger, Markus A. and Veening, Jan-Willem and Perez, Camilo. (2022) Mechanistic basis of choline import involved in teichoic acids and lipopolysaccharide modification. Science Advances, 8 (9). eabm1122.
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Official URL: https://edoc.unibas.ch/87998/
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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.
Faculties and Departments: | 05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Perez) |
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UniBasel Contributors: | Bärland, Natalie and Cebrero, Gonzalo Felipe and Perez, Camilo |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | American Association for the Advancement of Science |
ISSN: | 2375-2548 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Language: | English |
Identification Number: |
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edoc DOI: | |
Last Modified: | 09 Mar 2022 11:57 |
Deposited On: | 09 Mar 2022 11:57 |
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