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

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. (2021) Mechanistic basis of choline import involved in teichoic acids and lipopolysaccharide modification.

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Phosphocholine molecules decorating bacterial cell wall teichoic acids and outer-membrane lipopolysaccharide have significant 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) and hemicholinium-3. Our results provide novel 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)
UniBasel Contributors:Bärland, Natalie and Cebrero, Gonzalo Felipe and Perez, Camilo
Item Type:Preprint
Publisher:Cold Spring Harbor Laboratory
Number of Pages:35
Note:Publication type according to Uni Basel Research Database: Discussion paper / Internet publication
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Last Modified:22 Sep 2021 09:23
Deposited On:22 Sep 2021 09:23

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