Dr. Zhou received his B.S. (1988) from Peking University and PhD (1996) from the University of Oregon, Eugene. He worked as a postdoctoral fellow at the National Cancer Institute (1996-1999) and a professional research associate at the University of Colorado at Boulder (1999-2001). He worked for GeneFormatics, Inc. as a research scientist (2001-2003) in bioinformatics, structural biology and drug discovery before joining UCSB.
Our research efforts focus on using nuclear magnetic resonance (NMR) techniques to study protein structure, interactions, and dynamics. The power of NMR is explored with isotope labeling (13C,15N, and 2H) of the protein and by extending the nuclear spin-spin correlations into multi-dimensional space (2D, 3D and 4D) to gain more resonance dispersion. The type of spin-spin correlation explored is typically either through-bond or through space. This information allows sequential resonance assignments and 3D structure determination. Protein interactions with other molecules are studied by chemical shift perturbation mapping, saturation transfer experiments, linewidth analysis, or intermolecular NOEs. We measure properties of protein dynamics reflected in the rates of relaxation of nuclear spins (the return of a perturbed spin to equilibrium) on a residue by residue basis to better address how proteins function and interact with other molecules.
Currently we are working on several protein systems. One is proteins from the leucine-response regulatory system (lrp, papI) (in collaboration with David Low at MCDB and John Perona's groups). Lrp is a global regulator that controls the expression of a number of operons in response to leucine. PapI together with lrp and several other proteins controls the expression of surface pili-adhesin complexes. We are characterizing the solution structure of lrp and papI, their oligomerization states, and interactions among leucine, lrp, DNA, and papI. Other proteins we are working on include proteins from the chemotaxis signal transduction system (CheA, CheY, CheW, CheZ, etc.) and the nitrate-, nitrite-sensing system (NarL). Work is also underway in collaboration with Dr. Nobert Reich's group to address the phenomenon of correlated dynamics and its functional implications in mammalian DNA methyltransferase.
Selected Research Publications
Zhou, H. & Dahlquist, F.W. (1997) The phosphotransfer site of the chemotaxis-specific histidine autokinase CheA as revealed by NMR. Biochemistry 36, 699-710.
Zhou, H., Mazzulla, M.J., Stahl, S.J., Wingfield, P.T., Rubin, J.S., Bottaro, D.P., & Byrd, R.A. (1998) The solution structure of the N-terminal domain of hepatocyte growth factor reveals a potential heparin-binding site. Structure 6, 109-116.
Zhou, H., Vermeulen, A., Jucker, F. & Pardi, A. (2001). Incorporating residual dipolar couplings into the NMR solution structure determination of nucleic acids. Biopolymers 52, 168-80. Review.
Zhou H, Gallina M, Mao H, Nietlispach D, Betz SF, Fetrow JS, & Domaille PJ. (2003) 1H, 13C and 15N resonance assignments and secondary structure of the human protein tyrosine phosphatase, PRL-2. J. Biomol NMR. 27, 397-398.