Structural highlights
Function
[CPXR_ECOLI] Response regulator member of the two-component regulatory system CpxA/CpxR which responds to envelope stress response by activating expression of downstream genes including cpxP, degP, dsbA and ppiA (PubMed:7883164, PubMed:9401031). Binds and activates transcription from the degP promoter (PubMed:7883164); binding is enhanced by phosphorylation (PubMed:9401031). This system combats a variety of extracytoplasmic protein-mediated toxicities by increasing the transcription of the periplasmic protease, DegP in concert with sigma factor E (PubMed:7883164), as well as that of CpxP protein. Other downstream effectors may include SrkA (PubMed:23416055).[1] [2] [3]
Publication Abstract from PubMed
Bacterial two-component systems consist of a sensor histidine kinase (HK) and a response regulator (RR). HKs are homodimers that catalyze the autophosphorylation of a histidine residue and the subsequent phosphoryl transfer to its RR partner, triggering an adaptive response. How the HK autokinase and phosphotransferase activities are coordinated remains unclear. Here, we report X-ray structures of the prototypical HK CpxA trapped as a hemi-phosphorylated dimer, and of the receiver domain from the RR partner, CpxR. Our results reveal that the two catalytic reactions can occur simultaneously, one in each protomer of the asymmetric CpxA dimer. Furthermore, the increase of autokinase activity in the presence of phosphotransfer-impaired CpxR put forward the idea of an allosteric switching mechanism, according to which CpxR binding to one CpxA protomer triggers autophosphorylation in the second protomer. The ensuing dynamical model provides a mechanistic explanation of how HKs can efficiently orchestrate two catalytic reactions involving large-scale protein motions.
Structural Coupling between Autokinase and Phosphotransferase Reactions in a Bacterial Histidine Kinase.,Mechaly AE, Soto Diaz S, Sassoon N, Buschiazzo A, Betton JM, Alzari PM Structure. 2017 Jun 6;25(6):939-944.e3. doi: 10.1016/j.str.2017.04.011. Epub 2017, May 25. PMID:28552574[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dorsey-Oresto A, Lu T, Mosel M, Wang X, Salz T, Drlica K, Zhao X. YihE kinase is a central regulator of programmed cell death in bacteria. Cell Rep. 2013 Feb 21;3(2):528-37. doi: 10.1016/j.celrep.2013.01.026. Epub 2013, Feb 14. PMID:23416055 doi:http://dx.doi.org/10.1016/j.celrep.2013.01.026
- ↑ Danese PN, Snyder WB, Cosma CL, Davis LJ, Silhavy TJ. The Cpx two-component signal transduction pathway of Escherichia coli regulates transcription of the gene specifying the stress-inducible periplasmic protease, DegP. Genes Dev. 1995 Feb 15;9(4):387-98. PMID:7883164
- ↑ Raivio TL, Silhavy TJ. Transduction of envelope stress in Escherichia coli by the Cpx two-component system. J Bacteriol. 1997 Dec;179(24):7724-33. PMID:9401031
- ↑ Mechaly AE, Soto Diaz S, Sassoon N, Buschiazzo A, Betton JM, Alzari PM. Structural Coupling between Autokinase and Phosphotransferase Reactions in a Bacterial Histidine Kinase. Structure. 2017 Jun 6;25(6):939-944.e3. doi: 10.1016/j.str.2017.04.011. Epub 2017, May 25. PMID:28552574 doi:http://dx.doi.org/10.1016/j.str.2017.04.011
