Research Interests   Targeted protein degradation; Protein quality control; NMR spectroscopy

Research in the Walters laboratory is focused around providing dynamic pictures of how proteins interact with each other. Of special focus is the ubiquitin-proteasome pathway, which is well renowned for its role in targeted protein degradation. This system also participates in transcriptional regulation, apoptosis, DNA repair, immune response and cell cycle control. Malfunction of the ubiquitin-proteasome pathway is associated with neurological disorders, inflammatory processes and cancer. The Walters lab explores how key components of the ubiquitin-proteasome pathway interact to facilitate diverse cellular events. Towards this aim they have provided three-dimensional structures of the ubiquitin recognition proteins hHR23a (published in PNAS 2003) and S5a (published in J. Mol. Biol.). In addition they have defined how each of these proteins interacts with ubiquitin (published in Biochemistry 2003). Structural work in the Walters laboratory is performed in solution by using nuclear magnetic resonance (NMR) spectroscopy; a technology that is also used to determine the dynamic properties of biomolecules.

Recent Publications

Schreiner, P., Chen, X., Husnjak, K., Randles, L., Zhang, N., Elsasser, S., Finley, D., Dikic, I., Walters, K. J., Groll, M.: "Ubiquitin docking at the proteasome via a novel PH domain interaction," Nature 453, 548-552 (2008).

Husnjak, K., Elsasser, S., Zhang, N., Chen, X., Randles, L., Hofmann, K., Walters, K. J., Finley, D., Dikic, I.: "Proteasome subunit Rpn13 is a novel ubiquitin receptor," Nature 453, 481-488 (2008).

Kang, K., Chen, X., Lary, J. W., Cole, J. L., Walters, K. J.: "Defining how ubiquitin receptors hHR23a and S5a bind polyubiquitin," J. Mol. Biol. 369, 168-176 (2007).

Kang, Y., Zhang, N., Koepp, D. M., Walters, K. J.: "Ubiquitin receptor proteins hHR23a and hPLIC2 interact" J. Mol. Biol. 365 , 1093-1101 (2007).

Liu, F., Zhang, N., Zhou , X., Hanna, P. E., Wagner, C. R., Koepp, D. M., Walters, K. J.: "Protein aggregation and constitutive ubiquitylation of arylamine N-acetyltransferase" J. Mol. Biol. 361, 482-492 (2006).

Zhang, N., Liu, L., Liu, F., Wagner, C. R., Hanna, P. E., Walters, K. J.: "NMR-based model reveals the structural determinants of mammalian arylamine N-acetyltransferase substrate specificity" J. Mol. Biol. 363, 188-200 (2006).