Revisiting the pH-gated conformational switch on the activities of HisKA-family histidine kinases

MIDEROS MORA, MARÍA CRISTINA; Laura Miguel-Romero; Alonso Felipe-Ruiz; Patricia Casino; Alberto Marina

doi:10.1038/s41467-020-14540-5

Revisiting the pH-gated conformational switch on the activities of HisKA-family histidine kinases

Journal

Nature Communications

ISSN

2041-1723

Date Issued

2020-02-07

Author(s)

MIDEROS MORA, MARÍA CRISTINA

Facultad de Ciencias de la Salud Eugenio Espejo

Laura Miguel-Romero

Alonso Felipe-Ruiz

Patricia Casino

Alberto Marina

DOI

10.1038/s41467-020-14540-5

URL

https://cris.ute.edu.ec/handle/123456789/678

Abstract

AbstractHistidine is a versatile residue playing key roles in enzyme catalysis thanks to the chemistry of its imidazole group that can serve as nucleophile, general acid or base depending on its protonation state. In bacteria, signal transduction relies on two-component systems (TCS) which comprise a sensor histidine kinase (HK) containing a phosphorylatable catalytic His with phosphotransfer and phosphatase activities over an effector response regulator. Recently, a pH-gated model has been postulated to regulate the phosphatase activity of HisKA HKs based on the pH-dependent rotamer switch of the phosphorylatable His. Here, we have revisited this model from a structural and functional perspective on HK853–RR468 and EnvZ–OmpR TCS, the prototypical HisKA HKs. We have found that the rotamer of His is not influenced by the environmental pH, ruling out a pH-gated model and confirming that the chemistry of the His is responsible for the decrease in the phosphatase activity at acidic pH.