Structural Proteomics: annotating the genome using 3D structure
EMSL Project ID
2141
Abstract
One of the major conclusions of the completed and ongoing genome sequencing projects is that our understanding of biology is far from complete; a major proportion of the sequenced genes in higher organisms code for proteins of unknown function. Therefore, the major challenge facing biologists in the next decade will be to characterize all proteins in an organism (the proteome). Because a protein's biochemical function is determined by its 3-dimensional shape, structural biology will play a major role in proteomic research. However, function derives not from primary gene sequence but from three-dimensional protein structure. In many well documented cases, functional homology that escaped sequence analysis was revealed through structural analysis. From these observations emerged a theme of Structural Proteomics: three-dimensional structure is the fundamental unit of genomic information and a complete functional map of the proteome must ultimately consist of the three-dimensional structures for all proteins. Over the last year we and our collaborators (including those at EMSL) have shown that NMR spectroscopy is competitive with x-ray crystallography in the field of Structural Proteomics. We have solved the 3D structures of 10 proteins which in many cases identified or suggest biochemical functions that were later confirmed. Our aim in the future is to develop a platform technology that can be applied to the proteome of medically relevant organisms (prokaryotic and eukaryotic). We are currently finishing the proteome of M. thermoautotrophicum and have screened proteins that appear to be well folded and amenable for structure determination using NMR spectroscopy. Attached are the 15N-HSQC spectra of proteins we propose to study. This research is part of the Northeast Structural Genomics Consortium (NESG), an NIH-funded Center for structural genomics, and the Ontario program in Structural Proteomics.
Project Details
Project type
Capability Research
Start Date
2001-04-04
End Date
2001-07-24
Status
Closed
Released Data Link
Team
Principal Investigator