Jerome and Lorraine Aresty Chair and Professor II
Department of Molecular Biology and Biochemistry
Rutgers, The State University of New Jersey

Adjunct Professor
Department of Biochemistry
UMDNJ – Robert Wood Johnson Medical School

Northeast Structural Genomics Consortium

Cancer Institute of New Jersey

Ph.D., 1987, Cornell University

Telephone: (732) 235-5375
Fax: (732) 235-5779

Nuclear Magnetic Resonance (NMR) Laboratory Site
Northeast Structural Genomics (NESG) Consortium Site

Cancer biology, influenza virus, structural biology, and structural bioinformatics

As Director of the NIH-funded Northeast Structural Genomics Consortium (NESG) of the NIGMS Protein Structure Initiative, Dr. Montelione leads an inter-institutional project in large-scale structural proteomics and bioinformatics. Goals of our work involve developing high-throughput technologies suitable for determining many new protein structures from the human genome project using bioinformatics, nuclear magnetic resonance spectroscopy (NMR) and X-ray crystallography. These structures provide important insights into the functions of novel gene products identified by genomic and/or bioinformatic analysis. The resulting knowledge of structure and biochemical function provides the basis for collaborations with academic laboratories and pharmaceutical companies to develop drugs useful in treating human diseases that are targeted to these newly discovered functions. The success of our approach relies on our abilities to identify, clone, express and analyze several hundred biologically interesting proteins per year; only a fraction of the initial sequences chosen for cloning and analysis result in high-resolution 3D structures. However, this “funnel” process is yielding three-dimensional structures and new functions for some 200 proteins per year, and can thus have tremendous scientific impact. The NESG project has deposited more than 900 3D protein structures into the Protein Data Bank since its inception in the year 2000. Hypothesis-driven research areas enabled by this infrastructure and collaborations with other biologists include studies of protein complexes involved in influenza virus infection and innate immune response, networks of interacting proteins associated with human cancer biology, and ubiquitination pathways.

Figure 1. Alkyltransferase-like proteins (ATLs) are a novel class of DNA repair proteins related to O(6)-alkylguanine-DNA alkyltransferases (AGTs) that tightly bind alkylated DNA and shunt the damaged DNA into the nucleotide excision repair pathway. Our solution NMR structure of a bacterial ATL (cyan) provides further evidence for the conserved role of ATLs in this primordial mechanism.

Selected Publications

Raman S, Lange OF, Rossi P, Tyka M, Wang X, Aramini J, Liu G, Ramelot TA, Eletsky A, Szyperski T, Kennedy MA, Prestegard J, Montelione GT, Baker D (2010) NMR structure determination for larger proteins using backbone-only data. Science 327:1014-8

Huang YJ, Hang D, Lu LJ, Tong L, Gerstein MB, Montelione GT (2008) Targeting the human cancer pathway protein interaction network by structural genomics. Molecular & Cellular Proteomics 7:2048-60

Das K, Ma LC, Xiao R, Radvansky B, Aramini J, Zhao L, Marklund J, Kuo RL, Twu KY, Arnold E, Krug RM, Montelione GT (2008) Structural basis for suppression of a host antiviral response by influenza A virus. Proceedings of the National Academy of Sciences of the United States of America 105:13093-8

Yin C, Khan JA, Swapna GV, Ertekin A, Krug RM, Tong L, Montelione GT (2007) Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses. Journal of Biological Chemistry 282(28):20584-92

Aramini JM, Rossi P, Anklin C, Xiao R, Montelione GT (2007) Microgram-scale protein structure determination by NMR. Nature Methods 4(6):491-3

Aramini JM, Tubbs JL, Kanugula S, Rossi P, Ertekin A, Maglaqui M, Hamilton K, Ciccosanti CT, Jiang M, Xiao R, Soong TT, Rost B, Acton TB, Everett JK, Pegg AE, Tainer JA, Montelione GT (2010) Structural basis of O6-alkylguanine recognition by a bacterial alkyltransferase-like DNA repair protein. Journal of Biological Chemistry 285:13736-41