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TitleMechanistic basis of teichoic acid transport by a gatekeeper flippase.
Journal, issue, pagesbioRxiv, Year 2026
Publish dateFeb 23, 2026
AuthorsGonzalo Cebrero / Amrutha H Chidananda / Eric Cester / Julien Dénéréaz / Elif Sena Demir / Alen T Mathew / D Ryan Bhowmik / Mario de Capitani / Jean-Louis Reymond / Natarajan Kannan / Fikri Y Avci / Jan-Willem Veening / Ahmad Reza Mehdipour / Camilo Perez
PubMed AbstractThe cell wall is a complex structure that protects bacteria from environmental threats. Phosphocholine-containing teichoic acids are key cell wall biopolymers critical for host colonization, immune ...The cell wall is a complex structure that protects bacteria from environmental threats. Phosphocholine-containing teichoic acids are key cell wall biopolymers critical for host colonization, immune evasion, competence, and persistence in . The flippase TacF, a member of the multidrug/oligosaccharide-lipid/polysaccharide (MOP) superfamily, monitors the phosphocholine content of teichoic acids during transport, yet the underlying mechanism of this process remains unknown. We present a cryo-EM structure of TacF in lipid nanodiscs. complementation assays and molecular dynamics simulations reveal key residues involved in teichoic acid recognition and transport, while coevolutionary and conservation analyses delineate common mechanistic elements among MOP flippases, indicating a shared mechanism for polyprenyl-diphosphate-linked oligosaccharide lipid transport. Our findings provide mechanistic insights into an essential flippase involved in pathogenesis and a potential drug target.
External linksbioRxiv / PubMed:41808984 / PubMed Central
MethodsEM (single particle)
Resolution3.63 Å
Structure data

72367

9xzn

EMDB-72367, PDB-9xzn:
Teichoic acid flippase TacF from Streptococcus pneumoniae
Method: EM (single particle) / Resolution: 3.63 Å

Source
  • escherichia coli (E. coli)
  • Homo sapiens (human)
  • streptococcus pneumoniae (bacteria)
KeywordsMEMBRANE PROTEIN / Teichoic acid / Flippase / Transporter / Lipid transport

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