In bacteria, molecular oxygen (O2) serves as a key positional signal that controls lifestyle changes such as biofilm formation, a switch to a non-replicative state, nitrogen fixation, and production of alternative oxidases. In mammals oxygen, nitric oxide (NO), and carbon monoxide (CO) regulate neurotransmission, vascularization, vasodilation, and many other processes. Our research aims to understand mechanisms of regulation by oxygen and other physiological heme ligands. We focus on signal-transducing heme proteins that couple a sensory heme-binding domain (e.g. PAS, GAF, modified globin) to a transmitter. Such transmitter regions include the histidine-protein kinases of the two-component class, DNA-binding domains of the basic helix-loop-helix and helix-turn-helix classes, and the GGDEF/EAL-class diguanylate cyclase and c-di-GMP phosphodiesterases. Projects in our laboratory include examining the range and specificity of the signal-detection systems, the mechanisms of coupling of the sensors to their transmitters, and the key structural features of the detection and transduction functions. Approaches routinely used by our group include molecular-genetic manipulations, measurements of enzyme and ligand-binding kinetics spanning microseconds to hours, and spectroscopic determinations of local and global protein structures.
RESEARCH INTERESTS
Biochemistry, biophysics, and molecular genetics of signal transduction
Biological heme-based sensors
Signal-transducing kinases, cyclases, and phosphodiesterases
PAS-domains, GAF-domains, and sensory globins
Protein engineering
RECENT PUBLICATIONS
E. H. S. Sousa, J. R. Tuckerman, G. Gonzalez, and M. A. Gilles-Gonzalez, "DosT and DevS are oxygen-switched kinases in Mycobacterium tuberculosis." Protein Science, 16:1708-1709, 2007
E. H. S. Sousa, J. R. Tuckerman, G. Gonzalez, and M. A. Gilles-Gonzalez, "A memory of oxygen binding explains the dose response of the heme-based sensor FixL." Biochemistry, 46:6249-6257, 2007
M. A. Gilles-Gonzalez, G. Gonzalez, E. H. S. Sousa, and J. R. Tuckerman, "Oxygen-sensing histidine-protein kinases: assays of ligand binding and response-regulator turnover rates" Meth. Enzymol., 437:173-189, 2008
X. Wan, J. R. Tuckerman, J. A. Saito, T. A. K. Freitas, J. S. Newhouse, J. R. Denery , M. Y. Galperin, G. Gonzalez, M. A. Gilles-Gonzalez, and M. Alam, "Globins synthesize the second messenger c-di-GMP in bacteria." J. Mol. Biol., 388:262-270, 2009
J. R. Tuckerman, G. Gonzalez, E. H. S. Sousa, X. Wan, J. A. Saito, M. Alam, and M. A. Gilles-Gonzalez, "An oxygen-sensing diguanylate cyclase and phosphodiesterase couple for c-di-GMP control." Biochemistry, In press 2009
SIGNIFICANT PUBLICATIONS
M. A. Gilles-Gonzalez and G. Gonzalez, "Heme-based sensors: defining characteristics, recent developments, and regulatory hypotheses." J. Inorg. Biochem., 99:1-22, 2005
C. M. Dunham, E. M. Dioum, J. R. Tuckerman, G. Gonzalez, W. G. Scott, and M. A. Gilles-Gonzalez, "A distal arginine in oxygen-sensing heme-PAS domains is essential to ligand binding, signal transduction, and structure" Biochemistry, 42:7701-7708, 2003
G. Gonzalez, E. M. Dioum, C. M. Bertolucci, T. Tomita, M. Ikeda-Saito, M. R. Cheesman, N. J. Watmough, and M. A. Gilles-Gonzalez, "Nature of the displaceable heme-axial residue in the EcDos protein, a heme-based sensor from Escherichia coli" Biochemistry, 41:8414-8421, 2002
Delgado-Nixon, V.M., Gonzalez, G., and Gilles-Gonzalez, M.A., "Dos, a heme-binding PAS protein from Escherichia coli is a direct oxygen sensor." Biochemistry, 39:2685-2691, 2000
J. R. Tuckerman, G. Gonzalez, and M. A. Gilles-Gonzalez, "Complexation precedes phosphorylation for two-component regulatory system FixL/FixJ of Sinorhizobium meliloti" J. Mol. Biol., 308:449-455, 2001
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