| Author |
Molnar, Kathleen S. Bonomi, Massimiliano Pellarin, Riccardo Clinthorne, Graham D. Gonzalez, Gabriel Goldberg, Shalom D. Goulian, Mark Sali, Andrej DeGrado, William F. |
| Description |
Author Affiliation: Molnar KS ( Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA); Bonomi M ( Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.); Pellarin R ( Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.); Clinthorne GD ( Pharmacological Sciences Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.); Gonzalez G ( Biochemistry and Molecular Biophysics Graduate Group19104, USA, University of Pennsylvania, Philadelphia, PA 19104, USA); Goldberg SD ( Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA.); Goulian M ( Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.); Sali A ( Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.); DeGrado WF ( Department of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: william.degrado@ucsf.edu.) |
| Abstract |
Bacteria transduce signals across the membrane using two-component systems (TCSs), consisting of a membrane-spanning sensor histidine kinase and a cytoplasmic response regulator. In gram-negative bacteria, the PhoPQ TCS senses cations and antimicrobial peptides, yet little is known about the structural changes involved in transmembrane signaling. We construct a model of PhoQ signal transduction using Bayesian inference, based on disulfide crosslinking data and homologous crystal structures. The data are incompatible with a single conformation but are instead consistent with two interconverting structures. These states differ in membrane depth of the periplasmic acidic patch and the reciprocal displacement of diagonal helices along the dimer interface. Studies of multiple histidine kinases suggest this repacking might be a common mode of signal transduction in sensor His-kinase receptors. Because a similar scissors model has been ruled out in CheA-linked chemoreceptors, the evidence suggests that sensor His-kinase and CheA-linked receptors possess different signaling mechanisms. |
| Subject Keyword |
Discipline Molecular Biology Discipline Biochemistry Discipline Biotechnology Bacterial Proteins Chemistry Cystine Protein Kinases Physiology Bayes Theorem Computer Simulation Models, Molecular Protein Structure, Secondary Protein Structure, Tertiary Structural Homology, Protein Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Research Support, U.s. Gov't, Non-p.h.s. |
