Email: rmweis@chemistry.umass.edu
R. Weis Chemistry Dept Website

Ph.D.: Stanford University
Postdoctoral Training: University of Californian at Berkeley Honors: Beckman Young Investigator

Transmembrane Signaling, Physical Chemistry of Cell Membranes and Protein-Protein Interactions

A common feature of transmembrane receptor proteins is the dimeric or, more generally, oligomeric organization of subunits in the membrane. Clustering receptors together either as stable oligomers or in response to ligand binding will permit the system to exhibit cooperative and polyvalent interactions that have important consequences for transmembrane signaling and transport. For example, in the chemosensory system of Escherichia coli, we have found that receptor methylation occurs as an interdimer process. Analysis of methyltransferase-receptor interactions revealed that the transferase interacts with receptors at two separate locations, the sites of methylation, and the receptor c-terminus. The latter site functions as a tethering site that allows the transferase to methylate neighboring receptor subunits, and suggests that the proximity between receptor subunits may play a role in regulating methylation.

The chemosensory system of Escherichia coli, and through collaboration, other sensory and transport systems, are studied with regard to these issues using a combination of molecular biology, biochemistry, and biophysics.

Representative publications:

L. Kott, E. H. Braswell, A. L. Shrout, and R. M. Weis . 2003. Distributed subunit interactions in CheA contribute to dimer stability: a sedimentation equilibrium study. Biochim. Biophys. Acta. doi:10.1016/j.bbapap.2003.10.001 (in press).

A. L. Shrout, D. J. Montefusco, and R. M. Weis . 2003. Template-directed assembly of receptor signaling complexes. Biochemistry. 42, 13379-13385.

R. M. Weis , T. Hirai, A. Chalah, M. Kessel, P. J. Peters, and S. Subramaniam. 2003. Electron microscopic analysis of membrane assemblies formed by the bacterial chemotaxis receptor Tsr. J. Bacteriol. 185, 3636-3643.

Yi, X. and R. M. Weis (2002). "The receptor docking segment and S-adenosyl-L-homocysteine bind independently to the methyltransferase of bacterial chemotaxis." Biochim Biophys Acta 1596(1): 28-35.

Murphy, O. J., 3rd, X. Yi, R. M. Weis and L. K. Thompson (2001). "Hydrogen exchange reveals a stable and expandable core within the aspartate receptor cytoplasmic domain." J Biol Chem 276(46): 43262-9.

Li, G. and R. M. Weis (2000). "Covalent modification regulates ligand binding to receptor complexes in the chemosensory system of Escherichia coli." Cell 100(3): 357-65.

Rao, J., L. Yan, J. Lahiri, G. M. Whitesides, R. M. Weis and H. S. Warren (1999). "Binding of a dimeric derivative of vancomycin to L-Lys-D-Ala-D-lactate in solution and at a surface." Chem Biol 6(6): 353-9.

Rao, J., Lahiri, J., Isaacs, L., Weis, R.M. and Whitesides, G.M. (1998) A trivalent system from vancomycin•d-ala-d-ala with higher affinity than avidin•biotin. Science 280, 708-711.

Li, J., Li, G. and Weis, R.M. (1997) The serine chemoreceptor from Escherichia coli is methylated through an interdimer process.
Biochemistry 36, 11851-11857.

Seeley, S.K., Wittrock, G.K., Thompson, L.K. and Weis, R.M. (1996) Oligomers of the cytoplasmic fragment from the Escherichia coli aspartate receptor dissociate through an unfolded transition state. Biochemistry 35, 16336-16345.

Wu, J., Li, J., Li, G., Long, D.G. and Weis, R.M. (1996) The receptor binding site for the methyltransferase of bacterial chemotaxis is distinct from the sites of methylation. Biochemistry 35, 4984-4993.