Dr. Dahlquist received a Ph.D. From the California Institute of Technology in 1969. He was a Miller Research Fellow with Daniel E. Koshland, Jr at the University of California. Dr. Dahlquist joined the faculty at UCSB in 2004 after beginning his teaching and research career at the Department of Chemistry and the Institute of Molecular Biology at the University of Oregon. He is currently Chair of the Department of Chemistry and Biochemistry.
Our research group is interested in the relationships between protein structure and function. While the investigation of this question is not restricted to any specific technique, nuclear magnetic resonance offers a particularly useful and powerful approach to the problem and is relied on heavily. Several molecular systems are under investigation. For instance, one problem is how the dynamics of a protein are related to its structure and thermodynamic stability. Another concerns how extra-cellular information is gathered and utilized by protein complexes to generate signals that regulate biochemical activity inside the cell.
Our major area of interest is the phenomenon of chemotaxis in bacteria. When E. coli are placed in concentration gradients of certain chemicals, they either accumulate at the high concentration (for attractants) or low concentration (for repellents) regions of the gradient. The bacteria sense temporal changes in the concentration of attractant or repellent molecules and change their swimming behavior accordingly. This process requires sensing the concentrations of attractant or repellent, behavioral response to rapid changes in these concentrations and relatively slow adaptation to the new concentrations, which returns the swimming behavior to the unstimulated condition. Adaptation is associated with the reversible methylation of four transmembrane receptors. These proteins receive environmental information from outside the membrane and transmit that information to the cytoplasm. The interests of the laboratory are in defining how environmental information is transmitted across the inner membrane and how that information is used to control the activity of a specialized protein kinase (CheA) that interacts with the receptors via an adapter protein (CheW). One (CheY) of the two substrates of the kinase plays a central role in modulating the sense of rotation of the flagellar rotary motors. We are using NMR and other methods to understand the structures, dynamics and interactions of the proteins involved in this signaling system.
We continue to collaborate with other UCSB research groups to use NMR and other physical methods to monitor events in intrinsically unstructured proteins, recognition pathways of nucleic acid methyl transferases, and regulation of gene expression in bacteria and higher organisms.
Selected Research Publications
Peterson D.W., Ando D.M., Taketa D.A., Zhou H., Dahlquist F.W, Lew J.
No difference in kinetics of tau or histone phosphorylation by CDK5/p25 versus CDK5/p35 in vitro. Proc. Natl. Acad. Sci U S A., 2010, 107, 2884-9.
Pavlova, A., McCarney, E.R., Peterson, D.W., Dahlquist, F.W., Lew, J., Han, S.
Site-specific dynamic nuclear polarization of hydration water as a generally applicable approach to monitor protein aggregation. Phys. Chem. Chem. Phys. 2009, 11, 6833-9.
Zhou, H., Purdy, M.M., Dahlquist, F.W. and Reich, N.O. The recognition pathway for the DNA cytosine methyltransferase M.HhaI, Biochemistry, 2009, 48, 7807-16.
Hao, S, Zhou, H-J, and Dahlquist, F.W., The structural basis for the localization of the chemotaxis phosphatase CheZ by CheA short, J. Bact. 191, 2009, 5824-4.
Dyer, C.M. Vartanian AS, Zhou H, and Dahlquist, F.W. A molecular mechanism of bacterial flagellar motor switching, J. Mol. Biol., 2009, 388, 71-84. 2009
Peterson, D.,Zhou, H., Dahlquist, F.W., and Lew, J. ,Demonstration of a soluble oligomer of tau associated with fiber formation, Biochemistry, 2008, 47, 7393-404.
Caballero-Manrique, E., Bray, J. K. , Dahlquist, F. W. and Guenza, M. G. Bridging time scales in the dynamics of the signal transduction protein CheY: a theory of protein dynamics to predict N.M.R. relaxation, Biophysical J., 2007, 93, 4128-40.
Peterson, S.N., Dahlquist, F.W. and Reich, N., The role of high affinity nonspecific DNA binding by Lrp in transcriptional regulation and DNA organization. J. Mol. Bio, 2007, 369, 1307-1317.
Park, MJ, Dahlquist, FW, Doyle FJIII, Mathematical modeling and analysis of chemotaxis in Escherichia coli, IET Systems Biology. ,2007, 1, 222-229.
Zhou, H., Shatz,W., Purdy, M.M, Fera, N., Dahlquist, F.W., and Reich, N., Long range structural and dynamical changes induced by cofactor binding in DNA methyltransferase M.HhaI, Biochemistry, 2007, 46, 7261-8, 2007
Lundstrom, P., Vallurupalli, P., Religa, T., Dahlquist, F.W. and Kay, L.E. A single quantum methyl relaxation dispersion experiment with improved sensitivity, J. Biomol. NMR. 2007, 38, 79-88.
Kawamura, T., Le, U.K., Zhou, H., Dahlquist, F.W. Solution Structure of PapI, a key regulator of pap pili phase variation., J. Mol. Biol. ,2007, 365,1130-42.
Hamel, D., Zhou, H., Starich , M. R., Byrd, A. and Dahlquist, F.W. Chemical shift perturbation mapping of the phosphotransfer and catalytic domain interaction in the histidine autokinase CheA , Biochemistry, 2006, 45, 9509-17.
Dyer CM and Dahlquist, FW, Switched or Not? Structure of Unphosphorylated CheY Bound to the N-Terminus of FliM, J. Bact., 2006, 188, 7354-7363.