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Abstract
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 Streptococcus pneumoniae. 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 S. pneumoniae TacF in lipid nanodiscs. In vivo 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 S. pneumoniae pathogenesis and a potential drug target.

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MLA
Cebrero, Gonzalo, et al. “Mechanistic Basis of Teichoic Acid Transport by a Gatekeeper Flippase.” BioRxiv, 2026, doi:10.64898/2026.02.22.707263.
APA
Cebrero, G., Chidananda, A. H., Cester, E., Dénéréaz, J., Demir, E. S., Thykkoottathil Mathew, A., … Perez, C. (2026). Mechanistic basis of teichoic acid transport by a gatekeeper flippase. https://doi.org/10.64898/2026.02.22.707263
Chicago author-date
Cebrero, Gonzalo, Amrutha H. Chidananda, Eric Cester, Julien Dénéréaz, Elif Sena Demir, Alen Thykkoottathil Mathew, D. Ryan Bhowmik, et al. 2026. “Mechanistic Basis of Teichoic Acid Transport by a Gatekeeper Flippase.” BioRxiv. https://doi.org/10.64898/2026.02.22.707263.
Chicago author-date (all authors)
Cebrero, Gonzalo, Amrutha H. Chidananda, Eric Cester, Julien Dénéréaz, Elif Sena Demir, Alen Thykkoottathil Mathew, D. Ryan Bhowmik, Mario de Capitani, Jean-Louis Reymond, Natarajan Kannan, Fikri Y Avci, Jan-Willem Veening, Ahmadreza Mehdipour, and Camilo Perez. 2026. “Mechanistic Basis of Teichoic Acid Transport by a Gatekeeper Flippase.” BioRxiv. doi:10.64898/2026.02.22.707263.
Vancouver
1.
Cebrero G, Chidananda AH, Cester E, Dénéréaz J, Demir ES, Thykkoottathil Mathew A, et al. Mechanistic basis of teichoic acid transport by a gatekeeper flippase. bioRxiv. 2026.
IEEE
[1]
G. Cebrero et al., “Mechanistic basis of teichoic acid transport by a gatekeeper flippase,” bioRxiv. 2026.
@misc{01KJYSS9FVD3H0G2KNSRBZDAHM,
  abstract     = {{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 Streptococcus pneumoniae. 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 S. pneumoniae TacF in lipid nanodiscs. In vivo 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 S. pneumoniae pathogenesis and a potential drug target.}},
  author       = {{Cebrero, Gonzalo and Chidananda, Amrutha H. and Cester, Eric and Dénéréaz, Julien and Demir, Elif Sena and Thykkoottathil Mathew, Alen and Bhowmik, D. Ryan and de Capitani, Mario and Reymond, Jean-Louis and Kannan, Natarajan and Avci, Fikri Y and Veening, Jan-Willem and Mehdipour, Ahmadreza and Perez, Camilo}},
  language     = {{eng}},
  series       = {{bioRxiv}},
  title        = {{Mechanistic basis of teichoic acid transport by a gatekeeper flippase}},
  url          = {{http://doi.org/10.64898/2026.02.22.707263}},
  year         = {{2026}},
}

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