Faculty

Helen Jane Dyson 
Professor
Department of Molecular Biology
TSRI - 1984

Education 
Ph.D., University of Sydney 1977

Research Focus 
NMR is the method of choice in studying unfolded proteins, as well as proteins such as the prion protein that have highly unstructured parts. Since many of the entries in the published genomes appear to code for proteins that should be intrinsically unstructured, an understanding of the nature and behavior of unfolded proteins is assuming increasing importance.

Studies with unfolded and partly folded forms of proteins have given us important insights into the earliest steps in the protein folding process. A series of forms of the helical protein apomyoglobin, modeling various stages in the folding process, have now been fully characterized. Using NMR and other spectroscopic techniques, we have been able to map the progressive compaction and increasing structure formation that occurs as the protein folds. A series of mutant proteins has provided important, sometimes surprising, details of the folding process at the level of individual amino acid residues.

Probing the mechanism of action of enzymes using NMR techniques that give information on local motion in the polypeptide chain has given us important insights into the role of dynamics in enzyme action. We have studied several systems, including the clinically important antibiotic-resistance enzyme metallo-b-lactamase from Bacteroides fragilis and Escherichia coli thioredoxin. Structure-function studies are particularly focused on the role of polypeptide chain dynamics in a number of systems that appear to use thiol-disulfide chemistry to control cellular processes.

Selected References 
Intrinsically unstructured proteins and their functions. H.J. Dyson and P.E. Wright (2005). Nature Rev. Mol. Cell Biol. 6, 197-208.

Role of specific hydrophobic regions in initiating protein folding. H.J. Dyson, P.E. Wright, H.A. Scheraga (2006) Proc. Natl. Acad. Sci. USA 103, 13057-13061.

Hierarchical folding mechanism of apomyoglobin revealed by ultra-fast H/D exchange coupled with 2D NMR T. Uzawa, C. Nishimura, S. Akiyama, K. Ishimori, S. Takahashi, H. J. Dyson and P. E. Wright (2008) Proc. Natl. Acad. Sci. USA 105, 13859-13864..

Transfer of flexibility between ankyrin repeats in IkBa upon formation of the NF-kB complex. S.-C. Sue, C. Cervantes, E.A. Komives and H.J. Dyson (2008) J. Mol. Biol. 380, 917-931.