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Ann M. Stock
Professor
RWJMS-UMDNJ & HHMI
Dept of Biochemistry & Molecular Biology
CABM - Room 338
679 Hoes Lane
Piscataway, NJ 08854-5627
(732) 235-4844
FAX - 5289
stock@cabm.rutgers.edu |
Structure/function analysis of signal transduction proteins
The
goal of research in our laboratory is to understand the molecular mechanisms
of receptor-mediated signal transduction. In particular, research is focused
on elucidating structure/function relationships in proteins involved in
information processing using a combination of molecular genetic,
biochemical, and X-ray crystallographic methods. Specific interest is
directed toward investigating the role of covalent modifications of proteins
in signaling pathways. A large fraction of bacterial signal transduction
systems commonly known as two-component systems utilize a common mechanism
involving transfer of a high-energy phosphoryl group from a histidine
protein kinase to an aspartate residue of a response regulator protein. The
regulatory domains of the response regulator proteins can be thought of as
phosphorylation-activated switches that are turned on and off by
phosphorylation and dephosphorylation. In the active, phosphorylated state,
the conserved regulatory domains interact productively with other protein
domains to activate specific effector functions such as flagellar rotation,
regulation of transcription, or enzymatic catalysis. We have solved the
crystal structures of several representative members of the response
regulator family. These structures and correlated biochemical studies have
provided insight into the mechanism of function of response regulators.
Phosphorylation alters the conformation of the regulatory domain and the
altered molecular surface is exploited for regulatory protein-protein
interactions.
Current efforts are focused on extending our understanding of the molecular
mechanisms of regulation of response regulator function to systems-level
analysis of specific two-component signaling systems in bacterial cells. Our
efforts are focused both on model regulatory systems in E. coli and on
signaling systems involved in virulence of the human pathogen
Staphylococcus aureus.
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