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Visualizing autophosphorylation in histidine kinases

DOI: 10.1038/ncomms4258 DOI Help
PMID: 24500224 PMID Help

Authors: Patricia Casino (Instituto de Biomedicina de Valencia (IBV-CSIC) and Institut de Biologı ´a Molecular de Barcelona (IBMB-CSIC)) , Laura Miguel-romero (Instituto de Biomedicina de Valencia (IBV-CSIC)) , Alberto Marina (Instituto de Biomedicina de Valencia (IBV-CSIC) and CIBER de enfermedades raras (CIBERER))
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 5

State: Published (Approved)
Published: February 2014
Diamond Proposal Number(s): 8035

Abstract: Reversible protein phosphorylation is the most widespread regulatory mechanism in signal transduction. Autophosphorylation in a dimeric sensor histidine kinase is the first step in two-component signalling, the predominant signal-transduction device in bacteria. Despite being the most abundant sensor kinases in nature, the molecular bases of the histidine kinase autophosphorylation mechanism are still unknown. Furthermore, it has been demonstrated that autophosphorylation can occur in two directions, cis (intrasubunit) or trans (intersubunit) within the dimeric histidine kinase. Here, we present the crystal structure of the complete catalytic machinery of a chimeric histidine kinase. The structure shows an asymmetric histidine kinase dimer where one subunit is caught performing the autophosphorylation reaction. A structure-guided functional analysis on HK853 and EnvZ, two prototypical cis-and trans-phosphorylating histidine kinases, has allowed us to decipher the catalytic mechanism of histidine kinase autophosphorylation, which seems to be common independently of the reaction directionality.

Journal Keywords: Signal Transduction; Two-Component; Histidine Kinase; Autophosphorylation

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

Instruments: I24-Microfocus Macromolecular Crystallography

Other Facilities: ESRF, Grenoble, Franc. Beamline ID29