Deciphering the molecular mechanism of the bacterial division motor TolQRA

The Tol-Pal system is essential for maintaining outer membrane (OM) stability during cell division in Gram-negative bacteria. The inner membrane complex TolQRA harnesses proton motive force (PMF) to establish transient interactions within the periplasm, thereby coordinating cell envelope remodeling and facilitating OM invagination at division sites. However, the precise mechanism remains unclear. Here, we present cryo-electron microscopy structures of Escherichia coli TolQRA in multiple conformational states at 2.92-3.52 Å resolution, revealing rotary dynamics within the complex. Computational simulations reveal a proton-conductive channel comprising the putative proton-accepting residue Asp23 and the conserved polar residues Thr145 and Thr178, with monitored inter-residue distances providing support for a proton-driven rotary mechanism. Site-directed mutagenesis combined with functional assays validates the AlphaFold-predicted structure of the periplasmic domains of TolR and TolA, and further pinpoints critical residues required for complex function. Together, these findings advance our understanding of TolQRA-mediated proton transduction and offer new avenues for antibiotic drug development.

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Publication Details

Journal
Cell Discovery
Published
2025-11-04
DOI
https://doi.org/10.1038/s41421-025-00841-w
Citations
2
Primary Topic
Bacterial Genetics and Biotechnology
Type
article
Field-Weighted Citation Impact
3.63

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article

Deciphering the molecular mechanism of the bacterial division motor TolQRA

Bi‐Sen Ding, Chongrong Shen, Xiaodi Tang, Teng Xie et al.
2 citations
Cell Discovery
Bacterial Genetics and Biotechnology
3.63
article

Deciphering the molecular mechanism of the bacterial division motor TolQRA

Bi‐Sen Ding, Chongrong Shen, Xiaodi Tang, Teng Xie, Xinglong Dong, Haohao Dong, Shenghai Chang, Juqian Zhang, Yongbo Luo, Ruhong Zhou, Zhaoming Su, Xin Wang, Zhibo Zhang, Fangyuan Zhao, Binwu Ying, Wei Chi, Jie Pang
article en
2 citations

Abstract

The Tol-Pal system is essential for maintaining outer membrane (OM) stability during cell division in Gram-negative bacteria. The inner membrane complex TolQRA harnesses proton motive force (PMF) to establish transient interactions within the periplasm, thereby coordinating cell envelope remodeling and facilitating OM invagination at division sites. However, the precise mechanism remains unclear. Here, we present cryo-electron microscopy structures of Escherichia coli TolQRA in multiple conformational states at 2.92-3.52 Å resolution, revealing rotary dynamics within the complex. Computational simulations reveal a proton-conductive channel comprising the putative proton-accepting residue Asp23 and the conserved polar residues Thr145 and Thr178, with monitored inter-residue distances providing support for a proton-driven rotary mechanism. Site-directed mutagenesis combined with functional assays validates the AlphaFold-predicted structure of the periplasmic domains of TolR and TolA, and further pinpoints critical residues required for complex function. Together, these findings advance our understanding of TolQRA-mediated proton transduction and offer new avenues for antibiotic drug development.

Cell DiscoveryVol. 11(1)
Sichuan University (CN), Sir Run Run Shaw Hospital (CN), Shanghai Advanced Research Institute (CN), Institute for Advanced Study (DE), Southern Medical University Shenzhen Hospital (CN), First Affiliated Hospital Zhejiang University (CN), State Key Laboratory of Biotherapy, Zhejiang University (CN), Columbia University (US)
National Natural Science Foundation of China, Zhejiang University, Sichuan University, West China Hospital, Sichuan University
Openalex Percentile: Top 6%
Bacterial Genetics and Biotechnology
3.63
DOIOpen Access PDFOpenAlex
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