NMR Comes of Age with Nobel Recognition

"Nuclear magnetic resonance (NMR) has long been in the shadow of crystallography," says Peter Wright, Cecil H. and Ida M. Green Investigator in Medical Research and chair of the Department of Molecular Biology at The Scripps Research Institute (TSRI).

The 2002 Nobel Prize in Chemistry should change that. It was awarded to Kurt Wüthrich for "his development of nuclear magnetic resonance spectroscopy for determining the three-dimensional structure of biological macromolecules in solution."

Of the two primary methods for determining the three-dimensional structure of biological macromolecules—x-ray crystallography and NMR—crystallography is older by several decades. NMR exploded on the scene in the early 1980s as a viable technique for biomolecular structure determination when Wüthrich worked out the methodologies needed to solve the first protein structures using NMR.

Around the same time that Wüthrich was beginning to solve his first structures with the method, NMR was arriving at TSRI with Wright and Professor H. Jane Dyson, who came to the institute in 1984. NMR has been a part of the structural biology research at TSRI ever since.

"The NMR group here is incredibly strong," says Wright. "And we have one of the biggest and best-equipped NMR facilities in the world."

The principle NMR structural biologists at TSRI are:

H. Jane Dyson, who uses NMR to study the protein-folding process and the nature and behavior of unfolded and partly folded forms of proteins, including prion proteins and several newly-discovered, intrinsically unstructured proteins.

Mirko Hennig, who develops new NMR methodology to study the structure and dynamics of RNA and RNA–protein complexes. Mirko is particularly interested in using novel isotope labeling methodology in conjunction with tailored NMR experiments to provide new avenues to determine the structure of very large RNA molecules.

James R. Williamson, who studies the structure and dynamics of RNA molecules and RNA-protein complexes involved in the regulation of gene expression by employing NMR spectroscopy and X-ray crystallography for solving high-resolution three-dimensional structures and examining the mechanism of assembly of multiprotein-RNA complexes.

Peter Wright, who uses high-resolution, multi-dimensional, hetero-nuclear NMR spectroscopy to study protein and enzyme dynamics, protein folding, and molecular recognition. In particular, his laboratory solves structures of many protein-DNA and protein-protein complexes involved in the regulation of transcription.

Kurt Wüthrich, who develops NMR methodologies, pioneering the new techniques of transverse relaxation-optimized spectroscopy NMR (TROSY) and cross-correlated relaxation-enhanced polarization transfer (CRINEPT), which extend several-fold the size limit of structures that can be solved with NMR. In addition, he solves many structures of biological molecules—including pheromone, prion, and membrane proteins.

"Kurt's prize is extremely important because it is recognition for NMR as a method for determining the structures of biological macromolecules in solution," says Wright. "It really puts the field on the map, and having him join the group of NMR structural biologists at TSRI brings additional strength to what was already a world-class operation."

Wüthrich is Cecil H. and Ida M. Green Visiting Professor of Structural Biology in the Department of Molecular Biology at The Scripps Research Institute (TSRI); a member of TSRI's Skaggs Institute for Chemical Biology; and Professor of Biophysics at Eidgenössische Technische Hochschule Zürich (ETHZ) in Switzerland.

 

 

 


TSRI is home to the most powerful NMR magnet ever constructed, the 900 MHz. "We have one of the biggest and best-equipped NMR facilities in the world," notes TSRI investigator Peter Wright. Photo by Jason S. Bardi.