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The Northeast Structural Genomics Consortium (NESG) is one of four PSI:Biology High-Throughput Structure Determination
Centers and is a multi-institutional network
of over 100 investigators in the US, Germany, and Canada. Under the leadership of Gaetano Montelione, Professor of Molecular Biology & Biochemistry at
Rutgers University (pictured, right), NESG employs both X-Ray Crystallography and NMR Spectroscopy to determine the three-dimensional
structures of novel proteins. Over the past 12 years, the NESG has solved over 1,100 protein structures and contributed data and methods for every step of the protein
structure determination pathway. For example, NESG has provided protocols for sample production, extensive raw and processed NMR and crystallographic data,
structure/function annotations, and thousands of homology models derived from these solved structures.
One of the major communication tools and outreach projects of the NESG is the NESG NMR Wiki, a wiki-based web interface for sharing NMR data collection and analysis protocols between the NMR groups of NESG and with the broader scientific community. “The web site serves to not only develop standardized NMR data collection and analysis protocols consistently across the consortium,” Montelione said, “but also as a way for the NMR community to see how the NESG approaches NMR data collection and analysis.” The NESG NMR researchers frequently update this page with detailed descriptions of new technology developments. Professor Montelione stated that in addition to using this powerful instrument for sharing technology between the many groups in the consortium, it is used as a tool for training new staff and educating students.
Each PSI large-scale center has partnerships with biological researchers to enable studies in specific areas using high-throughput methods and techniques that are in place at the center. NESG is collaborating with the Mitochondrial Protein Partnership (MPP) under the leadership of John Markley at the University of Wisconsin-Madison and the Chaperone-Enabled Studies of Epigenetic Regulation Enzymes, led by Anthony Kossiakoff of the University of Chicago. These partnerships give biological investigators access to the resources and expertise of a large-scale center to solve the structures of their targets, such as the human mitochondrial inner membrane protein fragment shown here. At the same time, the Center has the opportunity broaden its expertise by working with new classes of proteins and developing technologies that are of interest to the wider biological community, such as new expression vectors and in vitro biotinylation protocols. In addition to these partnerships, NESG continues work on biologically themed projects, such as the Human Cancer Protein Interaction Network (HCPIN). To date, 78 structures have been solved from this network, including 4 protein-protein complexes. “The long-range goal of HCPIN,” said Montelione, “is to provide a comprehensive 3D structure-function database of cancer associated proteins and protein complexes in the context of their interaction networks.” This effort to complement and enrich cancer systems biology, as well as the work done with the biological partners, underscores the continuing contributions of the NESG to eukaryotic structural genomics and structural biology.
An overview of advances made by NESG in other areas of protein structure determination by NMR are mentioned in our Featured Technology Archive: Leveraging the Power of Molecular Fragment Replacement to Solve Protein Structures by NMR. This feature introduces methods developed by NESG to automate NMR structure anaylsis and solve structures of proteins with sparse NMR data. More recently, this restrained CS-Rosetta method has been refined for determining high-quality 3D structures of proteins in the 25-40 kDa size range using NMR data obtained on perdeuterated protein samples (Lange, et al., 2012).
Posted August 2012.