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Annu Rev Microbiol. 2019 Jun 21. doi: 10.1146/annurev-micro-091018-054627. [Epub ahead of print]

Two-Component Sensing and Regulation: How Do Histidine Kinases Talk with Response Regulators at the Molecular Level?

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Laboratory of Molecular and Structural Microbiology, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay; email: ,
Integrative Microbiology of Zoonotic Agents, Department of Microbiology, Institut Pasteur, Paris 75015, France.


Perceiving environmental and internal information and reacting in adaptive ways are essential attributes of living organisms. Two-component systems are relevant protein machineries from prokaryotes and lower eukaryotes that enable cells to sense and process signals. Implicating sensory histidine kinases and response regulator proteins, both components take advantage of protein phosphorylation and flexibility to switch conformations in a signal-dependent way. Dozens of two-component systems act simultaneously in any given cell, challenging our understanding about the means that ensure proper connectivity. This review dives into the molecular level, attempting to summarize an emerging picture of how histidine kinases and cognate response regulators achieve required efficiency, specificity, and directionality of signaling pathways, properties that rely on protein:protein interactions. α helices that carry information through long distances, the fine combination of loose and specific kinase/regulator interactions, and malleable reaction centers built when the two components meet emerge as relevant universal principles. Expected final online publication date for the Annual Review of Microbiology Volume 73 is September 9, 2019. Please see for revised estimates.

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