Our research aims to understand mechanisms of regulation by molecular oxygen and other physiological heme ligands. In bacteria oxygen is a key regulator of nitrogen fixation, production of alternative oxidases, and biofilm formation. In mammals oxygen, nitric oxide (NO), and carbon monoxide (CO) regulate neurotransmission, vascularization, vasodilation, and many other processes. We focus on signal-transducing heme proteins that couple a sensory heme-binding domain (e.g. PAS, GAF) to a transmitter. Such transmitter domains include the histidine-protein kinases of the two-component class, DNA-binding domains of the basic helix-loop-helix class, and the bacterial cyclic di-GMP cyclases and phosphodiesterases. Projects in our laboratory include examining, for three different classes of heme-based sensors, the range and specificity of their signal-detection systems, the mechanisms of sensory heme-binding domains to their transmitter partners, and the key structural features of their 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 and phosphodiesterases
PAS-domain and GAF-domain proteins
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
O. Moksvin, S. Kaplan, M. A. Gilles-Gonzalez, and M. Gomelsky, "Novel heme-based oxygen sensor with a revealing evolutionary history" J. Biol. Chem., Manuscript M703261200 July 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:In press., 2007
M. A. Gilles-Gonzalez, A. I., Caceres, E. H. S. Sousa, D. R. Tomchick, C. Brautigam, C. Gonzalez, and M. Machius, "A proximal arginine R206 participates in switching of the Bradyrhizobium japonicum FixL oxygen sensor" J. Mol. Biol., 360:80-89, 2006
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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