7PAF

Streptococcus pneumoniae choline importer LicB in lipid nanodiscs

Summary for 7PAF

• Entry DOI: 10.2210/pdb7paf/pdb
• EMDB information: 13268
• Descriptor: Nanobody, LicB protein, (1S)-2-{[{[(2R)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL STEARATE (3 entities in total)
• Functional Keywords: importer, choline, nanodisc, nanobody, transport protein
• Biological source: synthetic construct; More
• Total number of polymer chains: 4
• Total formula weight: 97651.01

Authors

Perez, C.,Baerland, N. (deposition date: 2021-07-29, release date: 2022-03-16, Last modification date: 2024-11-06)

Primary citation

Barland, N.,Rueff, A.S.,Cebrero, G.,Hutter, C.A.J.,Seeger, M.A.,Veening, J.W.,Perez, C.
Mechanistic basis of choline import involved in teichoic acids and lipopolysaccharide modification.
Sci Adv, 8:eabm1122-eabm1122, 2022

PubMed 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. is a prominent pathogen where phosphocholine decoration plays a fundamental role in virulence. Here, we present cryo-electron microscopy and crystal structures of 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: 35235350
DOI: 10.1126/sciadv.abm1122

Experimental method

ELECTRON MICROSCOPY (3.75 Å)