Specificity in Two-Component Signal Transduction Pathways

Abstract

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions. In the prototypical two-component system, a sensor histidine kinase catalyzes its autophosphorylation and then subsequently transfers the phosphoryl group to a response regulator, which can then effect changes in cellular physiology, often by regulating gene expression. The utility of these signaling systems is underscored by their prevalence throughout the bacterial kingdom and by the fact that many bacteria contain dozens, or sometimes hundreds, of these signaling proteins. The presence of so many highly related signaling proteins in individual cells creates both an opportunity and a challenge. Do cells take advantage of the similarity between signaling proteins to integrate signals or diversify responses, and thereby enhance their ability to process information? Conversely, how do cells prevent unwanted cross-talk and maintain the insulation of distinct pathways? Here we address both questions by reviewing the cellular and molecular mechanisms that dictate the specificity of two-component signaling pathways.

Induction of the pneumococcal vncRS operon by lactoferrin is essential for pneumonia

“…Following host invasion, pneumococci are exposed to the host’s serum. The TCSs are autophosphorylated upon contact with the ligand [3]. Therefore, this study aimed to identify whether the autophosphorylation of TCSs occur after the VncS sensor kinase senses signals from the host serum.…”

“…However, these proteins are also linked to virulence [2]. Bacteria can adapt to environmental changes using their TCSs [3]; however, the simple inactivation of the TCS may not substantially attenuate virulence owing to the redundancies in the regulatory systems. Additionally, which TCS plays a pivotal role in bacterial virulence is not completely understood.…”

Determinants of specificity in two-component signal transduction

“…This process of pathway insulation following duplication has resulted in extant organisms harboring large sets of two-component pathways that can transduce signals without significant cross-talk [4,11,40]. Consistently, an examination of the specificity residues in two-component proteins from an individual organism typically reveals significant differences in almost all possible pairwise comparisons of kinases or regulators [37].…”

“…In most cases these mechanisms enforce specific, oneto-one relationships between kinases and their cognate regulators. There are, however, some cases of branched pathways with physiologically-relevant one-to-many or many-to-one connectivity [4].…”

“…Strikingly, most bacteria encode dozens, if not hundreds, of two-component pathways for responding to a diverse range of signals [2,3]. The faithful coupling of input signals to desired cellular outputs requires tight enforcement of pathway specificity [4]. Here we review recent progress in elucidating the molecular basis of this specificity.…”