In recent years, "molecular chaperone" proteins have been recognized as essential for cellular viability and cellular response to various types of stress. These proteins participate in such diverse activities as protein folding and suppression of misfolding, polypeptide targeting to organells, protein denaturation\degradation, and oligomer disassembly. Our lab pursues structure-function studies on several molecular chaperone systems.
The DEA(D\H)-box RNA helicases are a family of proteins which participate in folding\rearranging the secondary and tertiary structure of specific RNAs. They participate in such diverse activities as RNA splicing, initiation of mRNA translation into polypeptides, ribosome assembly, and RNA degradation, to name a few. These proteins share a conserved helicase "core" which is ~400 amino acid residues in size.
SurA is a periplasmic molecular chaperone that is thought to facilitate the folding/assembly of outer membrane proteins in gram-negative bacteria.
Universal Stress Protein (UspA)
The universal stress protein, UspA, is a small, cytoplasmic bacterial protein whose expression is enhanced severalfold when cellular viability is challenged with heat shock, nutrient starvation, stress agents which arrest cell growth, or DNA-damaging agents. UspA enhances the rate of cell survival during prolonged exposure to such conditions, suggesting it asserts a general "stress endurance" activity. However, the biochemical mechanism by which it protects cells from a broad spectrum of stress agents is unknown.
The discovery of ribozymes (RNA enzymes) raised the intriguing questions (i) how do certain RNA sequence motifs form structures that catalyzes specific chemical reactions, and (ii) what are the chemical mechanisms of these reactions?.
Microbial pathogens assert virulence through a spectrum of factors, or toxins. Structural studies of virulence factors provide a framework for understanding their mechasm, as well as for designing inhibitors targeted toward them.