Bacterial sensor evolved by decreasing complexity
Edited by Ann Stock, Rutgers Robert Wood Johnson Medical School Department of Biochemistry and Molecular Biology, Piscataway, NJ; received May 20, 2024; accepted December 19, 2024 by Editorial Board Member Thomas J. Silhavy
Significance
Many bacterial receptors contain multimodular sensing domains indicative of complex sensory processes. The presence of more than one sensing module likely permits the integration of multiple signals, although the molecular detail and functional relevance for these complex sensors remain poorly understood. Bimodular sensory domains are often considered to have arisen from the fusion or duplication of monomodular domains. Evolution by increasing complexity is generally believed to be a dominant force. Here, we suggest the opposite—how a monomodular sensing domain may have evolved from a bimodular one. Our findings will thus motivate research to establish whether evolution by decreasing complexity is typical of other sensory domains.
Abstract
Bacterial receptors feed into multiple signal transduction pathways that regulate a variety of cellular processes including gene expression, second messenger levels, and motility. Receptors are typically activated by signal binding to ligand-binding domains (LBDs). Cache domains are omnipresent LBDs found in bacteria, archaea, and eukaryotes, including humans. They form the predominant family of extracytosolic bacterial LBDs and were identified in all major receptor types. Cache domains are composed of either a single (sCache) or a double (dCache) structural module. The functional relevance of bimodular LBDs remains poorly understood. Here, we identify the PacF chemoreceptor in the phytopathogen Pectobacterium atrosepticum that recognizes formate at the membrane-distal module of its dCache domain, triggering chemoattraction. We further demonstrate that a family of formate-specific sCache domains has evolved from a dCache domain, exemplified by PacF, by losing the membrane-proximal module. By solving high-resolution structures of two family members in complex with formate, we show that the molecular basis for formate binding at sCache and dCache domains is highly similar, despite their low sequence identity. The apparent loss of the membrane-proximal module may be related to the observation that dCache domains bind ligands typically at the membrane-distal module, whereas studies have failed to find ligands bound in the membrane-proximal module. This work advances our understanding of signal sensing in bacterial receptors and suggests that evolution by reducing complexity may be a route for shaping diversity.
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Data, Materials, and Software Availability
The PacF-LBD models and their alignments with sCache structures data have been deposited in github (83). All study data are included in the article and/or supporting information.
Acknowledgments
This study was supported by Grants from the Spanish Ministry for Science and Innovation/Agencia Estatal de Investigación 10.13039/501100011033 (Grants PID2020-112612 GB-I00 and PID2023-146216NB-I00 to T.K., PID2019-103972GA-I00 and PID2023-146281NB-I00 to M.A.M., and PID2020-116261 GB-I00 to J.A.G.), the Consejo Superior de Investigaciones Científicas (Grant 2024AEP062 to T.K.), the Junta de Andalucía (Grant P18-FR-1621 to T.K.), and the NIH (Grant R35GM131760 to I.B.Z.). We thank Raquel Vázquez Santiago for technical support.
Author contributions
M.A.M., I.B.Z., and T.K. designed research; E.M.-C., J.A.G., J.X., M.A.M., and F.V. performed research; E.M.-C., J.A.G., J.X., F.V., M.A.M., I.B.Z., and T.K. analyzed data; and J.A.G., M.A.M., I.B.Z., and T.K. wrote the paper.
Competing interests
The authors declare no competing interest.
Supporting Information
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Copyright © 2025 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Data, Materials, and Software Availability
The PacF-LBD models and their alignments with sCache structures data have been deposited in github (83). All study data are included in the article and/or supporting information.
Submission history
Received: May 20, 2024
Accepted: December 19, 2024
Published online: January 29, 2025
Published in issue: February 4, 2025
Keywords
Acknowledgments
This study was supported by Grants from the Spanish Ministry for Science and Innovation/Agencia Estatal de Investigación 10.13039/501100011033 (Grants PID2020-112612 GB-I00 and PID2023-146216NB-I00 to T.K., PID2019-103972GA-I00 and PID2023-146281NB-I00 to M.A.M., and PID2020-116261 GB-I00 to J.A.G.), the Consejo Superior de Investigaciones Científicas (Grant 2024AEP062 to T.K.), the Junta de Andalucía (Grant P18-FR-1621 to T.K.), and the NIH (Grant R35GM131760 to I.B.Z.). We thank Raquel Vázquez Santiago for technical support.
Author contributions
M.A.M., I.B.Z., and T.K. designed research; E.M.-C., J.A.G., J.X., M.A.M., and F.V. performed research; E.M.-C., J.A.G., J.X., F.V., M.A.M., I.B.Z., and T.K. analyzed data; and J.A.G., M.A.M., I.B.Z., and T.K. wrote the paper.
Competing interests
The authors declare no competing interest.
Notes
This article is a PNAS Direct Submission. A.M.S. is a guest editor invited by the Editorial Board.
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Bacterial sensor evolved by decreasing complexity, Proc. Natl. Acad. Sci. U.S.A.
122 (5) e2409881122,
https://doi.org/10.1073/pnas.2409881122
(2025).
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