Visualizing autophosphorylation in histidine kinases.
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.
1] Department of Genomic and Proteomic, Instituto de Biomedicina de Valencia (IBV-CSIC), Jaume Roig 11, 46010 Valencia, Spain [2] Department of Structural Biology, Institut de Biología Molecular de Barcelona (IBMB-CSIC), Baldiri Reixac, 4-8, Torre R, 3era Planta, 08028 Barcelona, Spain.
Patricia
P
Casino
Department of Genomic and Proteomic, Instituto de Biomedicina de Valencia (IBV-CSIC), Jaume Roig 11, 46010 Valencia, Spain.
Laura
L
Miguel-Romero
1] Department of Genomic and Proteomic, Instituto de Biomedicina de Valencia (IBV-CSIC), Jaume Roig 11, 46010 Valencia, Spain [2] CIBER de enfermedades raras (CIBERER), Valencia, Spain.
Alberto
A
Marina
D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D004252:DNA Mutational Analysis; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071677:Histidine Kinase; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D009097:Multienzyme Complexes; D011494:Protein Kinases; D000071677:Histidine Kinase; C057843:envZ protein, E coli