Structural Proteomics: annotating the genome using 3D structure
EMSL Project ID
2290
Abstract
A large proportion of the sequenced genes in many 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 13 proteins by NMR spectroscopy 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) and eventually proteins specifically involved in diseases such as cancer, that are discovered through DNA microarray technology. We have screened proteins from different organisms that appear to be well folded and amenable for structure determination using NMR spectroscopy. Attached are the 15N-HSQC spectra of these proteins. The ec302 is prophage cp4-57 regulatory protein AlpA from E. coli. It is homologous to a transcription regulator VC0497 found in V. cholerae and also to XF1786 protein from the plant pathogen X. fastidiosa. The ec394 is a hypothetical protein from E. coli and is conserved among different pathogenic organisms like H. influenzae, V. cholerae, and N. meningitidis. These proteins may be good drug targets against these pathogenic organisms and knowledge of its 3D structure would facilitate the design of the drugs. The mth0819 is a hypothetical protein from M. thermoautotrophicum, it is conserved among archea and its C-terminal part has sequence homology to a small part of the subtillisin-like proprotein convertase found in mouse and human. Knowledge of the 3 dimensional structure of these proteins may give us an insight into the function of the hypothetical proteins. We could also use these to homology model the other proteins that are difficult to get the structure of. 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
2001-10-01
End Date
2002-11-18
Status
Closed
Released Data Link
Team
Principal Investigator
Related Publications
Hlaing Oo WM, LV Saraf, MH Engelhard, V Shutthanandan, and MD Mccluskey. 2009. "Suppression of conductivity in Mn-Doped ZnO Thin Films." Journal of Applied Physics 105(1):013715. doi:10.1063/1.3063730
Johnson GE, CM Wang, TA Priest, and J Laskin. 2011. "Monodisperse Au11 Clusters Prepared by Soft Landing of Mass Selected Ions." Analytical Chemistry 83(21):8069-8072. doi:10.1021/ac202520p
L.V. Saraf, W.M.H. Oo, Z.H. Zhu, C.M. Wang, M.H. Engelhard, D.R. Baer and M.D. McCluskey, "Solubility and Secondary Phase Segregation Relationship for Favorable Vs Unfavorable Dopants in Oriented/Epitaxial ZnO Films Grown by MOCVD," Spring 2008 MRS abstract.