Structural and Biochemical Studies on Protein-Protein Interactions in GroEL-Mediated Protein Folding and Microbial Communications |
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Protein-protein interactions are ubiquitous and essential in biological processes; principles of these interactions are crucial to the understanding of protein folding process and cellular communications, including the cross-talk among the bacterial community and the uptake of pathogens into host cells. Our research goal is to understand the roles of protein-protein interactions in specific cellular processes, to elucidate the structural basis underlying specific protein functions, and to provide mechanistic insights into modulations of biological functions. To achieve this goal, we employ an array of biochemical and biophysical techniques, including molecular biology, combinatorial biology, and particularly X-ray crystallography.
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| GroEL-mediated protein folding | ||
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Recent papers: |
GroEL-mediated protein folding process. These projects are extensions of our ongoing work on the structure of GroEL-substrate interaction and the mechanism of GroEL-assisted protein folding. We solved structures of both the apical domain of GroEL and the tetradecameric GroEL complexed with a high affinity peptide, selected from a phage-display peptide library. These structures provide, for the first time, atomic-level resolution details addressing substrate binding to GroEL. We propose that structural plasticity of the peptide-binding site is one of the attributes responsible for the substrate diversity of GroEL. Our current and future research will focus on several issues, including 1) is there an alternative substrate-binding site in GroEL?; 2) does this peptide-binding site interact with peptides in other conformations?; 3) what is the cooperative effect in the multiple attachments of substrate to GroEL?; 4) how is substrate release to the GroEL central cavity coupled to the energetic of nucleotide binding and/or hydrolysis?
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| Quorum Sensing | ||
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Recent papers: Structural basis for antiactivation in bacterial quorum sensing.2007 PNAS 104 (42): 16474– 16479. |
Regulatory mechanism in the quorum-sensing system of Agrobacterium tumefaciens. Quorum sensing is a community behavior of bacteria that has evolved to coordinate a broad spectrum of biological functions, often involved with host interactions such as pathogenesis and symbiosis, in response to bacterial population density via signal molecules. For example, A. tumefaciens, a significant agricultural pathogen, uses a quorum sensing pathway to regulate the expression of genes involved in propagating the tumor-inducing (Ti) plasmid in order to infect plants. In this regulation, the signal molecule, acylated homoserine lactone, binds to and activates its receptor TraR, a transcription factor, and the transcription activity of TraR is antagonized by an anti-activator TraM through formation of theTraR-TraM complex. Our lab is interested in investigating the biochemical aspects and structural basis of this inhibitory mechanism; in particular, we have solved the crystal structure of the anti-activator TraM. In collaboration with Dr. Clay Fuqua, we hope to dissect the functional complexity of TraR and TraM in quorum-sensing pathway, and our studies will have a significant impact on the area of microbial cell-to-cell communication. |
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Copyright© Chen Research Group, Molecular and Cellular Biochemistry Department, Indiana University
Maintained by Melissa Illingworth (last updated January 9, 2012)