Scripps Research Joint Appointments

The Skaggs Institute for Chemical Biology
Faculty, Kellogg School of Science and Technology

Research Focus

Solution Structure And Dynamics Of Proteins

High-resolution nuclear magnetic resonance (NMR) spectroscopy is now firmly established as an essential tool in structural molecular biology. It provides both a unique method for three-dimensional structure determination and a powerful new approach for studies of protein dynamics and folding.

A major part of our research involves application of multi-dimensional heteronuclear NMR methods to obtain novel insights into processes of biomolecular recognition. Much of our effort is directed towards determination of the structures of protein-DNA and protein-protein complexes involved in the regulation of transcription. NMR is uniquely suited for studying molecular recognition processes because it can provide detailed information on structure, internal molecular dynamics, and hydration. In addition, we are using NMR to determine how protein dynamics is coupled to the catalytic activity of enzymes.

Protein folding is one of the central unsolved problems in structural biology. Multi-dimensional NMR spectroscopy has proven to be a powerful approach for characterization of the structure and dynamics of unfolded states of proteins and protein folding intermediates. Such studies are providing new insights into the fundamental mechanisms of protein folding and the basic rules by which the amino acid sequence codes for secondary structure. In addition, coupled with stopped flow methods, NMR provides unique opportunities for structural characterization of kinetic intermediates formed during folding.

Education

B.S., Chemistry, University of Auckland, 1968
M.S., Chemistry, University of Auckland, 1969
Ph.D., Chemistry, University of Auckland, 1972

Professional Experience

The Scripps Research Institute 1984-present, Professor and Chair, Department of Molecular Biology.

University of Sydney, 1976-1984, Faculty member, Department of Inorganic Chemistry

University of Oxford, 1972-76, Postdoctoral, Chemistry/Biochemistry

 

 

Awards & Professional Activities

New Zealand University Grants Committee Post-Graduate Scholar, 1969-1972
New Zealand University Grants Committee Postdoctoral Fellow, University of Oxford, 1972-1973
Endowed Chair: Cecil H. and Ida M. Green Investigator in Medical Research, 1987-present
NIH Merit Award, 1994-2001
Honorary Doctor of Medicine, Karolinska Institute, Stockholm, 1995
Elected to the American Academy of Arts and Sciences, 1995
Fellow, American Association for the Advancement of Science, 1998
Honorary Doctor of Science, The University of Sydney, 2003
Honorary Member, NMR Society of Japan, 2006
Leach Medal, 2008
Member, The National Academy of Sciences, 2008
Fellow, International Society of Magnetic Resonance, 2008
Honorary Member, Israel Chemical Society, 2009
The Stein and Moore Award, The Protein Society, 2010
American Chemical Society, San Diego Section, Distinguished Scientist Award, 2010

Selected References

Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d. B.P. Hudson, M.A. Martinez-Yamout, H.J. Dyson and P.E. Wright (2004) Nat. Struct. Biol., 11, 257-264.

The dynamic energy landscape of dihydrofolate reductase catalysis. D.D. Boehr, D. McElheny, H.J. Dyson and P.E. Wright (2006), Science 313, 1638-1642.

Mechanism of coupled folding and binding of an intrinsically disordered protein. K. Sugase, H.J. Dyson and P.E. Wright (2007), Nature 447, 1021-1027.

Modeling transient collapsed states of an unfolded protein to provide insights into early folding events. D.J. Felitsky, M.A. Lietzow, H.J. Dyson and P.E. Wright (2008) Proc. Natl Acad. Sci., USA, 105, 6278-6283.

Links

The Skaggs Institute for Chemical Biology

The Skaggs Institute Scientific Report

Folding Upon Binding: Unique Protein Activation Mechanism Found

Structure of Important Tumor Growth Protein--A Target for Cancer Therapy