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Updated: May 27, 2026

A Fluorescence-based Assay of Phospholipid Scramblase Activity
09:52

A Fluorescence-based Assay of Phospholipid Scramblase Activity

Published on: September 20, 2016

Mechanistic basis of teichoic acid transport by a gatekeeper flippase

Gonzalo Cebrero1,2, Amrutha H Chidananda3, Eric Cester3

  • 1Biozentrum, University of Basel, Basel, Switzerland.

Nature Communications
|May 25, 2026
PubMed

Insights

The flippase TacF is crucial for Streptococcus pneumoniae cell wall integrity and pathogenesis. This study reveals its structure and mechanism for transporting phosphocholine-containing teichoic acids, offering a potential drug target.

Area of Science:

  • Microbiology
  • Structural Biology
  • Biochemistry

Background:

  • The bacterial cell wall is vital for protection and survival.
  • Phosphocholine-containing teichoic acids are essential for Streptococcus pneumoniae virulence.
  • The TacF flippase's role in teichoic acid transport and its mechanism are poorly understood.

Purpose of the Study:

  • To elucidate the mechanism of the TacF flippase in Streptococcus pneumoniae.
  • To determine the structural basis for TacF's recognition and transport of teichoic acids.
  • To identify potential drug targets for combating S. pneumoniae infections.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine the structure of TacF.
  • In vivo complementation assays to assess TacF function.
  • Molecular dynamics simulations to analyze residue interactions.
  • Coevolutionary and conservation analyses to compare MOP superfamily flippases.

Main Results:

  • The cryo-EM structure of S. pneumoniae TacF in lipid nanodiscs was determined.
  • Key residues involved in teichoic acid recognition and transport by TacF were identified.
  • A shared mechanism for polyprenyl-diphosphate-linked oligosaccharide lipid transport among MOP flippases was proposed.

Conclusions:

  • The study provides mechanistic insights into TacF function in S. pneumoniae.
  • TacF plays a critical role in S. pneumoniae pathogenesis.
  • TacF represents a potential therapeutic target for treating S. pneumoniae infections.

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