Madhubrata Ghosh, Loo Chien Wang, Roland G. Huber, Yunfeng Gao, Leslie K. Morgan, Nikhil Kumar Tulsian, Peter J. Bond, Linda J. Kenney, Ganesh S. Anand, Engineering an Osmosensor by Pivotal Histidine Positioning within Disordered Helices, Structure, Volume 27, Issue 2, 2019, Pages 302-314.e4, ISSN 0969-2126, https://doi.org/10.1016/j.str.2018.10.012.
Abstract:
Histidine kinases (HKs) funnel diverse environmental stimuli into a single autophosphorylation event at a conserved histidine residue. The HK EnvZ is a global sensor of osmolality and cellular acid pH. In previous studies, we discovered that osmosensing in EnvZ was mediated through osmolyte-induced stabilization of the partially disordered helical backbone spanning the conserved histidine autophosphorylation site (His243). Here, we describe how backbone stabilization leads to changes in the microenvironment of His243, resulting in enhanced autophosphorylation through relief of inhibition and repositioning of critical side chains and imidazole rotamerization. The conserved His-Asp/Glu dyad within the partially structured helix is equally geared to respond to acid pH, an alternative environmental stimulus in bacteria. This high-resolution "double-clamp" switch model proposes that a His-Asp/Glu dyad functions as an integrative node for regulating autophosphorylation in HKs. Because the His-Asp/Glu dyad is highly conserved in HKs, this study provides a universal model for describing HK function.
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Funding Info:
This work was supported by grants from the Singapore Ministry of Education Academic Research Fund Tier 3 to G.S.A. (MOE2012-T3-1-008), the Research Centre of Excellence in Mechanobiology at the National University of Singapore, funded by the Ministry of Education, Singapore, and Veterans Affairs Grant IOBX-000372 and NIH AI-123640 to L.J.K.
Description:
The full paper is available for download at the publisher's URL here: https://doi.org/10.1016/j.str.2018.10.012