The Northeast Structural Genomics Consortium (NESG) is one of four Large-Scale Centers (LSCs) for structure production funded by the NIH NIGMS Protein Structure Initiative (PSI). The goals of the PSI LSCs are to (i) generate three-dimensional (3D) structures for large numbers of proteins selected using broad biological, genomic, and bioinformatics criteria, together with targets selected from specific biological theme projects, so as to provide significant structural coverage of a large number of protein sequences In nature, (ii) develop and disseminate novel and/or improved technologies for structural biology and bioinformatics, and (iii) make these structures, structure production data, and the associated reagents and technologies publicly available to the worldwide scientific community. In PSI:Biology, the next phase of the PSI program, the NESG will expand Its mission by carrying our collaborative structural genomics projects together with several PSI Consortia for High-Through-Put (HTP) Enabled Structural Biology Partnerships (Biology Partnerships) and associated Program Announcements (PARs). The primary goal of the NESG In PSI:Biology is to provide >1,100 new 3D protein structures to the Protein Data Bank (PDB) over 5 years, together with extensive raw and processed data, protocols for sample production, structure/function annotations, and thousands of homology models derived from these structures. This will complement the ~ 900 structures deposited by NESG in PSI Phases 1 and 2. In particular, NESG will provide novel 3D structural information useful in modeling large numbers of eukaryotic and human proteins. Our efforts will span five classes of target types: (i) proteins nominated In collaborations to be established with PSI Biology Partnerships, (ii) domain families (referred to as BIG, MEGA, and META families) defined by the central PSI:Biology Target Selection Subcommittee to provide course-grained coverage of large protein domain families;(iii) proteins defined by the NESG Biomedical Theme of 'Networks of Proteins Associated with Human Cancer and Developmental Biology';(iv) proteins nominated by the general biomedical research community, and (v) proteins selected for specific technology-development goals. Protein targets in the first two of these classes, representing ~ 80% of the overall NESG effort, will be selected in a coordinated process together with the other LSCs and Biology Partnerships so as to maximize biological impact and minimize redundant efforts. The many methods and technologies for structural genomics research developed in this project will provide the next- generation tools for traditional hypothesis-driven biological research, and will thus have powerful and broad impact on the infrastructure for biological science and engineering.

Public Health Relevance

The NESG consortium will make 3D structural information a routinely and broadly used component of biological research. The proposed program includes plans for training young scientists. We will provide structural coverage of hundreds of human proteins associated with cancer and developmental biology, as well as coverage of many eukaryotic protein domain families. This discovery research program will generate new technologies and novel specific biomedical hypotheses, along with the information and reagents needed for follow on functional studies, providing the basis for new R01-type research programs.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54GM094597-04
Application #
8507758
Study Section
Special Emphasis Panel (ZGM1-CBB-4 (HT))
Program Officer
Ainsztein, Alexandra M
Project Start
2010-09-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$7,311,352
Indirect Cost
$1,471,605
Name
Rutgers University
Department
Type
Schools of Medicine
DUNS #
001912864
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901
Zhu, Jiang; Li, Shuangli; Ramelot, Theresa A et al. (2018) Structural insights into the impact of two holoprosencephaly-related mutations on human TGIF1 homeodomain. Biochem Biophys Res Commun 496:575-581
Moremen, Kelley W; Ramiah, Annapoorani; Stuart, Melissa et al. (2018) Expression system for structural and functional studies of human glycosylation enzymes. Nat Chem Biol 14:156-162
Wang, Zi; Nie, Yao; Zhang, Kunxiao et al. (2018) Solution structure of SHIP2 SH2 domain and its interaction with a phosphotyrosine peptide from c-MET. Arch Biochem Biophys 656:31-37
Sachleben, Joseph R; Adhikari, Aashish N; Gawlak, Grzegorz et al. (2017) Aromatic claw: A new fold with high aromatic content that evades structural prediction. Protein Sci 26:208-217
Gao, Qi; Chalmers, Gordon R; Moremen, Kelley W et al. (2017) NMR assignments of sparsely labeled proteins using a genetic algorithm. J Biomol NMR 67:283-294
Zhu, Jiang; Wang, Huapu; Ramelot, Theresa A et al. (2017) Solution NMR structure of zinc finger 4 and 5 from human INSM1, an essential regulator of neuroendocrine differentiation. Proteins 85:957-962
Guan, Rongjin; Aiyer, Sriram; Cote, Marie L et al. (2017) X-ray crystal structure of the N-terminal region of Moloney murine leukemia virus integrase and its implications for viral DNA recognition. Proteins 85:647-656
Aalberts, Daniel P; Boël, Gregory; Hunt, John F (2017) Codon Clarity or Conundrum? Cell Syst 4:16-19
Marcos, Enrique; Basanta, Benjamin; Chidyausiku, Tamuka M et al. (2017) Principles for designing proteins with cavities formed by curved ? sheets. Science 355:201-206
Elnatan, Daniel; Betegon, Miguel; Liu, Yanxin et al. (2017) Symmetry broken and rebroken during the ATP hydrolysis cycle of the mitochondrial Hsp90 TRAP1. Elife 6:

Showing the most recent 10 out of 182 publications