Structural Proteomics:  Toward High-Throughput Structural Biology as a Tool in Functional Genomics

Adelinda Yee received her B.Sc. in Chemical Engineering from Mapua Institute of Technology (Philippines) and M.Sc. and Ph.D. in Chemistry from University of Manitoba. She carried out postdoctoral training with Dr. Arrowsmith studying DNA-binding proteins by NMR spectroscopy and is currently working with the structural proteomics project.

Keith Pardee received a B.Sc. in Plant Physiology from University of Alberta and an M.Sc. in Botany from University of British Columbia and is currently a Ph.D. candidate at the Department of Molecular and Medical Genetics at the University of Toronto.

Dinesh Christendat received his B.Sc. and Ph.D. from Concordia University. He carried out his postdoctoral training as part of this project and has now moved on to a faculty position in the Botany Department of the University of Toronto.

Alexei Savchenko received his B.Sc. and M.Sc. from Yerevan State University (Armenia) and Ph.D. in Molecular Biology/Microbiology from University of Nantes (France). He carried out his postdoctoral training at Michigan State University and is currently working with the structural proteomics project.

Aled Edwards received his B.Sc. and Ph.D. in Biochemistry from McGill University, Montreal. He is also carried out postdoctoral training at Stanford University and was an assistant professor at McMaster University before taking his current positions at the University of Toronto and the Ontario Cancer Institute in 1997.

Cheryl Arrowsmith received a B.Sc. in Chemistry from Allegheny College and a Ph.D. in chemistry from University of Toronto. She carried out postdoctoral training at Stanford University. Since 1992 she has been a Senior Scientist at the Ontario Cancer Institute and member of the Department of Medical Biophysics, University of Toronto.

Structural proteomics is the determination of atomic resolution three-dimensional protein structures on a genome-wide scale in order to better understand the relationship between protein sequence, structure, and function. Here we describe our ongoing structural proteomics project on the nonmembrane proteins of the archeaon, Methanobacterium thermoautotrophicum. This article provides a snapshot of an ongoing pilot project in an emerging area of multidisciplinary research that involves bioinformatics, molecular biology, biochemistry, and instrumental methods such as NMR spectroscopy and X-ray crystallography. An assessment of the technical challenges in this type of large-scale project along with a comparison of the efficiency of sample production for both X-ray crystallography and NMR spectroscopy will be discussed. Examples of new insights into protein function and the relationship between structure and sequence will also be presented.