Molecular basis of quorum-sensing signal transduction by CqsS and its inhibition by CqsA, the autoinducer synthase.
4 affiliations
- 1Department of Cardiology, The First Affiliated Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
- 2Ministry of Education Key Laboratory for Membraneless Organelles and Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
- 3Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
- 4HHMI, Chevy Chase, MD 20815.
Abstract
Vibrio bacteria possess multiple quorum-sensing systems, each of which conveys information into the cell concerning the cell density and species composition of the vicinal community. Germane to the present work is the CqsA-CqsS quorum-sensing pathway that vibrios use for intragenus communication. CqsA is the synthase for the autoinducer (S)-3-hydroxytridecan-4-one (CAI-1), and CqsS, a bifunctional two-component kinase-phosphatase, is the CAI-1 receptor. Here, we determine the cryo-EM structures of the full-length Vibrio harveyi CqsS dimer in the apo- and ATPγS-bound states. Our structures reveal the molecular basis for the initiation of the phosphorylation cascade, which we support through biochemical and genetic analyses. Autophosphorylation of CqsS occurs in cis at the conserved histidine residue (H1), whereas phospho-transfer to the conserved aspartate residue (D1) in the C-terminal receiver domain occurs in trans. By coexpressing CqsS and CqsA to capture CqsS bound to CAI-1, we unexpectedly find a tight interaction between the CqsS intracellular domain and CqsA. In the complex, the CqsS H1 residues are positioned away from the catalytic cavity, and CqsS kinase activity is inhibited. Cryo-EM analysis, focused on the transmembrane domain of CqsS in this complex, reveals the presence of two CAI-1 molecules. CAI-1 binding induces an obvious movement of transmembrane helix 6, disrupting its extension into the cytosol, providing a structural basis for how CAI-1 binding in the periplasm is coupled to signal transduction into the cytoplasm. Together, our findings advance the understanding of CqsS-CAI-1-mediated quorum-sensing signal transduction, an activity that underpins the coordination of group behaviors in vibrios.
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BibTeX
@article{liu2026molecular,
title = {{Molecular basis of quorum-sensing signal transduction by CqsS and its inhibition by CqsA, the autoinducer synthase.}},
author = {Mengchan Liu and Yufan Yang and Julie S Valastyan and Yuru Zhang and Grace A Beggs and Yanhong Liu and Zhenhua Wang and Bonnie L Bassler and Hongwu Qian},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = nov,
doi = {10.1073/pnas.2617274123},
url = {https://europepmc.org/article/MED/42970674},
note = {CC BY},
}
RIS
TY - JOUR
TI - Molecular basis of quorum-sensing signal transduction by CqsS and its inhibition by CqsA, the autoinducer synthase.
AU - Mengchan Liu
AU - Yufan Yang
AU - Julie S Valastyan
AU - Yuru Zhang
AU - Grace A Beggs
AU - Yanhong Liu
AU - Zhenhua Wang
AU - Bonnie L Bassler
AU - Hongwu Qian
PY - 2026
DA - 2026/11/02
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2617274123
UR - https://europepmc.org/article/MED/42970674
AB - Vibrio bacteria possess multiple quorum-sensing systems, each of which conveys information into the cell concerning the cell density and species composition of the vicinal community. Germane to the present work is the CqsA-CqsS quorum-sensing pathway that vibrios use for intragenus communication. CqsA is the synthase for the autoinducer (S)-3-hydroxytridecan-4-one (CAI-1), and CqsS, a bifunctional two-component kinase-phosphatase, is the CAI-1 receptor. Here, we determine the cryo-EM structures of the full-length Vibrio harveyi CqsS dimer in the apo- and ATPγS-bound states. Our structures reveal the molecular basis for the initiation of the phosphorylation cascade, which we support through biochemical and genetic analyses. Autophosphorylation of CqsS occurs in cis at the conserved histidine residue (H1), whereas phospho-transfer to the conserved aspartate residue (D1) in the C-terminal receiver domain occurs in trans. By coexpressing CqsS and CqsA to capture CqsS bound to CAI-1, we unexpectedly find a tight interaction between the CqsS intracellular domain and CqsA. In the complex, the CqsS H1 residues are positioned away from the catalytic cavity, and CqsS kinase activity is inhibited. Cryo-EM analysis, focused on the transmembrane domain of CqsS in this complex, reveals the presence of two CAI-1 molecules. CAI-1 binding induces an obvious movement of transmembrane helix 6, disrupting its extension into the cytosol, providing a structural basis for how CAI-1 binding in the periplasm is coupled to signal transduction into the cytoplasm. Together, our findings advance the understanding of CqsS-CAI-1-mediated quorum-sensing signal transduction, an activity that underpins the coordination of group behaviors in vibrios.
SN - 0027-8424
SN - 1091-6490
ER -