Associate Professor
Ph.D., Stanford University, 1996
Postdoctoral Fellow, Yale University, 1996-2000

Program Affiliation: Molecular Biology & Genetics | Microbiology

Research Groups Affiliation: Biochemistry | Cell Biology | Microbiology

Phone: 812/855-0491
Fax: 812/855-6082
Email Lingling

Chen Lab website

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.

1) 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?

2) 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 plant.   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 TraR-TraM complex.   Our lab is interesting 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.

Guozhou Chen, Phillip Jeffery, Clay Fuqua, Yigong Shi and Lingling Chen. Structural basis of TraM anti-activation of quorum sensing transcription factor TraR. Proc. Natl. Acad. Sci. USA, 104:16474-16479, 2007.

Banga, S., Gao, P., Shen, X., Fiscus, V., Zong, W., Chen, L., and Luo, Z. Legionella pneumophila inhibits macrophage apoptosis by targeting pro-death members of the Bcl2 protein family. Proc. Natl. Acad. Sci. USA 104:5121-5126, 2007.

Zhida Zheng, Guozhou Chen, Evan D. Brutinel, Timothy L. Yahr, and Lingling Chen. Biochemical characterization of a regulatory cascade controlling transcription of the Pseudomonas aeruginosa type III secretion system. J. Biol. Chem. 282:6136-6142, 2007.

Guozhou Chen, Chao Wang, Clay Fuqua, Lian-Hui Zhang and Lingling Chen. The crystal structure and mechanism of TraM2, a second quorum sensing
antiactivator of Agrobacterium tumefaciens strain A6. J. Bact. 188:8244-8251, 2006.

Lykken, G., Chen, G., Brutinel, E., Chen, L., and Yahr, T. Characterization of ExsC and ExsD self-association and heterocomplex formation. J. Bact. 188:6832-6840, 2006.

Wang, C., Zhang, H.-B., Chen, G., Chen, L, and Zhang, L.-H.. Dual Control of Quorum Sensing by Two TraM-Type Antiactivators in Agrobacterium tumefaciens Octopine Strain A6. Journal of Bacteriology, April 2006, p. 2435-2445, Vol. 188, No. 7

Chen, G., Malenkos, J., Cha, M., Fuqua, C. and Chen, L. 2004. Quorum-Sensing Antiactivator TraM Forms a Dimer That Dissociates to Inhibit TraR. Molecular Microbiology. Mol. Micro. 52: 1641-1651.

Wang J. and Chen L. 2003. Domain motions in GroEL upon binding of an oligopeptide. J Mol Biol. 334(3):489-99.

Chen, L. and Sigler, P. 1999. Crystal structure of a GroEL/peptide complex: Plasticity as a basis for substrate diversity. Cell, 99:757-768.

Chen, L., Wildegger, G., Kiefhaber, T., Hodgson, K. O., and Doniach, S. 1998. Kinetics of lysozyme refolding: Structural characterization of a non-specifically collapsed state using time-resolved X-ray scattering. J. Mol. Biol. 276:225-237.