title: Signal transduction in histidine kinases: insights from new structures.
abstract: Histidine kinases (HKs) are major players in bacterial signaling. There has been an explosion of new HK crystal structures in the last 5 years. We globally analyze the structures of HKs to yield insights into the mechanisms by which signals are transmitted to and across protein structures in this family. We interpret known enzymological data in the context of new structural data to show how asymmetry across the dimer interface is a key feature of signal transduction in HKs, and discuss how different HK domains undergo asymmetric to symmetric transitions during signal transduction and catalysis. A thermodynamic framework for signaling that encompasses these various properties is presented, and the consequences of weak thermodynamic coupling are discussed. The synthesis of observations from enzymology, structural biology, protein engineering, and thermodynamics paves the way for a deeper molecular understanding of HK signal transduction.
authors.affiliation: Department of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, 555 Mission Bay Boulevard South, Box 3122, San Francisco, CA 94158, USA.
authors.forename: Manasi P
authors.initials: MP
authors.lastname: Bhate
authors.affiliation: Department of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, 555 Mission Bay Boulevard South, Box 3122, San Francisco, CA 94158, USA; Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Molnar
authors.affiliation: Department of Biology and Department of Physics, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Goulian
authors.affiliation: Department of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, 555 Mission Bay Boulevard South, Box 3122, San Francisco, CA 94158, USA. Electronic address: william.degrado@ucsf.edu.
authors.forename: William F
authors.initials: WF
authors.lastname: DeGrado
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D019281:Dimerization; D000071677:Histidine Kinase; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013816:Thermodynamics
chemical_list: D011494:Protein Kinases; D000071677:Histidine Kinase