9quq
cryo-EM structure of TolQR conformation2 in SMA nanodiscs
Structural highlights
FunctionTOLA_ECOLI Involved in the TonB-independent uptake of group A colicins (colicins A, E1, E2, E3, and K). Necessary for the colicins to reach their respective targets after initial binding to the bacteria. Also involved in the translocation of bacteriophage DNA. Publication Abstract from PubMedThe 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 A 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. Deciphering the molecular mechanism of the bacterial division motor TolQRA.,Shen C, Xie T, Luo Y, Zhao F, Wang X, Zhang Z, Pang J, Zhang J, Dong X, Chang S, Ding BS, Ying B, Chi W, Su Z, Zhou R, Tang X, Dong H Cell Discov. 2025 Nov 4;11(1):87. doi: 10.1038/s41421-025-00841-w. PMID:41184225[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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