Mideros-Mora, C., Miguel-Romero, L., Felipe-Ruiz, A., Casino, P. and Marina, A. (2020) Revisiting the pH-gated conformational switch on the activities of HisKA-family histidine kinases. Nature Communications, 11, 769. (doi: 10.1038/s41467-020-14540-5) (PMID:32034139) (PMCID:PMC7005713)
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Abstract
Histidine 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.
| Item Type: | Articles |
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| Additional Information: | The following funding is acknowledged: Spanish Government (Ministerio de Economia y Competitividad; Grant no. BIO2016-78571-P to Alberto Marina; grant No. BFU2016-78606-P to Patricia Casino; contract No. RYC-2014-16490 to Patricia Casino); Valencian Government Prometeo program (grant No. II/2014/029 to A.M.). C.M.-M. is the recipient of a Ph.D. fellowship from the Programa de Becas, Secretaría de Educación Superior, Ciencia, Tecnología e Innovación of Ecuador Government (2015-AR2Q9228). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Miguel Romero, Dr Laura |
| Authors: | Mideros-Mora, C., Miguel-Romero, L., Felipe-Ruiz, A., Casino, P., and Marina, A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Nature Communications |
| Publisher: | Nature Research |
| ISSN: | 2041-1723 |
| ISSN (Online): | 2041-1723 |
| Copyright Holders: | Copyright © 2020 The Authors |
| First Published: | First published in Nature Communications 11:769 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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