Abstract

This chapter discusses the state of our understanding of two-component pathways on all levels, beginning with the initial input stimulus through the final output response. Its goal is to demonstrate the key principles and paradigms for how these signaling pathways work by drawing on specific, illustrative examples. Two-component signaling proteins are among the most prevalent signaling molecules in the bacterial kingdom and represent a primary means by which bacteria sense and respond to a range of stresses and environments. In many cases, histidine kinases are bifunctional: acting as both kinases and phosphatases for their cognate substrates. All histidine kinases have two conserved domains: the dimerization and phosphotransfer (DHp) domain and the catalytic and ATP-binding (CA) domain. Most bacteria are faced with a constantly changing environment and a multitude of stressors that challenge their survival. Two-component signaling proteins are one of the predominant means by which bacteria sense and respond to such challenges. Since their initial discovery two decades ago, histidine kinases and response regulators have been implicated in countless stress responses. But it remains a major challenge to understand how cells evolve new signaling pathways to respond to new stressors.

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