Mechanistic basis of teichoic acid transport by a gatekeeper flippase.
Publisher DOI
PubMed ID
42185287
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 unresolved. 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.
Date Issued
2026-05-25
Publication Type
Article
Subject(s)
Language(s)
en
Author(s)
Cebrero, Gonzalo | |
Chidananda, Amrutha H | |
Cester, Eric | |
Dénéréaz, Julien | |
Demir, Elif Sena | |
Mathew, Alen T | |
Bhowmik, D Ryan | |
Kannan, Natarajan | |
Avci, Fikri Y | |
Veening, Jan-Willem | |
Mehdipour, Ahmad Reza | |
Perez, Camilo |
Additional Credits
Journal
Nature Communications
Publisher
Nature Research
ISSN
2041-1723
Access(Rights)
open.access