Structural Proteomics: annotating the genome using 3D structure
EMSL Project ID
2583a
Abstract
We wish to understand protein biochemical function through the use of NMR spectroscopy and the derivation of solution structures from NMR data. The rationale for such an approach is that protein three-dimensional structure is a fundamental unit of genomic information and a complete functional map of the proteome must ultimately consist of the three-dimensional structures for all proteins. In the post genomic era NMR can help to achieve such a goal by:? Providing fundamental insights into the mechanism of action of proteins of known function.
? Suggesting functional roles for novel proteins of unknown function.
? Providing an experimental tool for the interpretation of functional data such as mutagenesis, protein-protein interaction studies and ligand binding analysis.
This project is a collaboration with Michael Kennedy at EMSL and includes both structural genomics protein targets as well as traditional hypothesis driven research grants from Canadian sources (Canadian Institutes for Health Research and National Cancer Institute of Canada). For both types of research we are also very interested in developing methods and strategies that will make protein structure determination by NMR faster and more efficient Our collaboration on data collection and analysis with Dr. Kennedy is particularly focussed on the latter. The wealth of structural informations that would come from the structural proteomics project could also enrich our understanding of protein folding and the evolutionary relationship between genomes. A table of the structures solved and the resulting publications which makes use of EMSL NMR spectrometers is attached. For the next period of spectrometer use at PNNL we will be studying the following targets:
In continuation of our structural proteomics project, we have screened proteins that appear to be well folded and amenable for structure determination using NMR spectroscopy. The lower field magnet time requested are for suites of experiments required for backbone resonance assignments while the higher field magnet time are for the CN-NOESY experiments. Attached are the 15N-HSQC spectra of some of these proteins.
(1) pa4608 is a hypothetical protein from Pseudomonas aeruginosa. It is conserved in many different pathogenic organism.
(2) mth1362 is a putative ferrous iron transport protein from Methanobacterium thermoautotrophicum. This protein has sequence homology to over 29 other proteins found in different prokaryotes. The resulting 3D structure of this protein can be used to model the other 29 proteins.
(3) ta1306 is another hypothetical protein from Thermoplasma acidophilum. This protein is also found in one other organism, Ferroplasma acidarmanus, that lives in extremely high salt condition.
Project Details
Project type
Capability Research
Start Date
2004-04-16
End Date
2005-01-26
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members