It is clear that growth and sporulation are inexorably intertwined in the most fundamental of cellular functions including chromosome replication and division but the mechanisms that join these processes are poorly, if at all, understood. This research program investigates regulatory connections between the coordination of cell growth and division and the basic mechanisms by which proteins evolve molecular recognition. This proposal investigates two-component signaling at several levels. A vital system, YycFG, required for homeostatic maintenance of cell wall and membrane components essential for growth is shown to be physically associated with the division mechanism and to receive and possibly coordinate signaling between division and cell wall synthesis. Protein:protein association in heterologous multiprotein complexes is one means for sharing information between processes and for amalgamating enzymes of biosynthetic pathways into super-molecular complexes. How proteins know who to assemble with is determined by interaction surface residues. In this proposal we apply our mathematical analyses of large sets of proteins deduced from genomic sequence databases to identify interaction surfaces to the problem of how biosynthetic pathways form large synthetic complexes. Despite the considerable evidence for the interweaving of regulatory controls for growth and sporulation, there is very little known f signals or mechanisms that decide between the two outcomes for cell division;growth or sporulation. New investigations are proposed in understanding sensor kinase regulation and to delve deeper into the regulatory connections with growth. The significance of this research is not limited to understanding the phosphorelay and sporulation in a corner of the bacterial world but has regulatory implications for signal transduction in eukaryotes and plants.
This proposal continues long term studies designed to understand how bacteria respond to environmental and cell cycle signals to promote growth, division, and development. Interference with these mechanisms is the basis for design of molecules to combat infectious disease.
|Szurmant, Hendrik; Hoch, James A (2013) Statistical analyses of protein sequence alignments identify structures and mechanisms in signal activation of sensor histidine kinases. Mol Microbiol 87:707-12|
|Procaccini, Andrea; Lunt, Bryan; Szurmant, Hendrik et al. (2011) Dissecting the specificity of protein-protein interaction in bacterial two-component signaling: orphans and crosstalks. PLoS One 6:e19729|
|Steiner, Elisabeth; Dago, Angel E; Young, Danielle I et al. (2011) Multiple orphan histidine kinases interact directly with Spo0A to control the initiation of endospore formation in Clostridium acetobutylicum. Mol Microbiol 80:641-54|
|Zhao, Haiyan; Volkov, Arsen; Veldore, Vidya Harini et al. (2010) Crystal structure of the transcriptional repressor PagR of Bacillus anthracis. Microbiology 156:385-91|
|Schug, Alexander; Weigt, Martin; Hoch, James A et al. (2010) Computational modeling of phosphotransfer complexes in two-component signaling. Methods Enzymol 471:43-58|
|Szurmant, Hendrik; Hoch, James A (2010) Interaction fidelity in two-component signaling. Curr Opin Microbiol 13:190-7|
|Lunt, Bryan; Szurmant, Hendrik; Procaccini, Andrea et al. (2010) Inference of direct residue contacts in two-component signaling. Methods Enzymol 471:17-41|
|Wilson, Adam C; Hoch, James A; Perego, Marta (2009) Two small c-type cytochromes affect virulence gene expression in Bacillus anthracis. Mol Microbiol 72:109-23|
|Fukushima, Tatsuya; Szurmant, Hendrik; Kim, Eun-Ja et al. (2008) A sensor histidine kinase co-ordinates cell wall architecture with cell division in Bacillus subtilis. Mol Microbiol 69:621-32|
|Szurmant, Hendrik; Bobay, Benjamin G; White, Robert A et al. (2008) Co-evolving motions at protein-protein interfaces of two-component signaling systems identified by covariance analysis. Biochemistry 47:7782-4|
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