4UHK

Crystal structure of the receiver domain of CpxR from E. coli (phosphorylated)

Summary for 4UHK

• Entry DOI: 10.2210/pdb4uhk/pdb
• Related: 4UHJ 4UHS 4UHT
• Descriptor: TRANSCRIPTIONAL REGULATORY PROTEIN CPXR, MAGNESIUM ION (3 entities in total)
• Functional Keywords: transcription
• Biological source: ESCHERICHIA COLI
• Cellular location: Cytoplasm : P0AE88
• Total number of polymer chains: 3
• Total formula weight: 46998.62

Authors

Mechaly, A.E.,Alzari, P.M.A. (deposition date: 2015-03-24, release date: 2016-04-13, Last modification date: 2017-06-21)

Primary citation

Mechaly, A.E.,Soto Diaz, S.,Sassoon, N.,Buschiazzo, A.,Betton, J.M.,Alzari, P.M.
Structural Coupling between Autokinase and Phosphotransferase Reactions in a Bacterial Histidine Kinase.
Structure, 25:939-944.e3, 2017

PubMed Abstract: 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.

PubMed: 28552574
DOI: 10.1016/j.str.2017.04.011

Experimental method

X-RAY DIFFRACTION (2.6 Å)