Mechanistic basis of teichoic acid transport by a gatekeeper flippase
Cebrero, G.; Chidananda, A. H.; Cester, E.; Denereaz, J.; Demir, E. S.; Mathew, A. T.; Bhowmik, D. R.; de Capitani, M.; Reymond, J.-L.; Kannan, N.; Avci, F.; Mehdipour, A. R.; Veening, J.-W.; Perez, C.
Show 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.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Structural Insights into Cir-mediated Killing by the Antimicrobial Protein Microcin V 97%
- Hexokinase-I directly binds to a charged membrane-buried glutamate of mitochondrial VDAC1 and VDAC2 96%
- Differences in the regulation mechanisms of the glutamine synthetase from methanogenic archaea unveiled by structural investigations 95%
Similar papers in this journal
- The high-energy transition state of a membrane transporter 97%
- Lipopolysaccharide lateral mobility in the Gram-negative bacterial outer membrane is confined and governed by interactions within the conserved Lipid A anchor 95%
- Virion morphology and on-virus spike protein structures of diverse SARS-CoV-2 variants 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.