Faculty

Gino Cingolani, Ph.D. Biochemistry and Molecular Biology 4239 Weiskotten Hall Upstate Medical University 750 East Adams Street Syracuse, NY 13210 (315) 464-8744

Education and Clinical Training

Research Program and Department Affiliations

Research Interests

Research Abstract

The main goal of my laboratory is to study the structure and function of large macromolecular machines at the atomic level. To achieve this goal we use a combination of X-ray crystallography and biophysical/biochemical techniques. In particular, we focus our research on two biological problems related to the transport of proteins and nucleic acids in and out the cell nucleus and to a class of large viral DNA pumps known as portal proteins.

Nucleo-cytoplasmic trafficking

Transport between the cytoplasm and nucleoplasm of eukaryotic cell occurs through the nuclear pore complex (NPC), a large structure spanning the nuclear envelope. In the past years many progresses have been made in identifying and characterizing the specific transport signals mediating the recognition of cellular cargoes by nuclear transport receptors of the importin b-superfamily. However, little is known about the three-dimensional structure of NPC proteins (also named nucleoporins) and how the interaction of these proteins with import/export complexes may drive translocation through the pore. We would like to solve the three dimensional structure of several nucleoporins in complex with transport receptors. This study will tremendously aid our understanding of the atomic structure of the NPC and shed light on the molecular mechanisms of translocation through the NPC as well as it will allow exploring new efficient ways to deliver exogenous molecules into the cell nucleus.

Large viral dsDNA pumps

Portal proteins form a family of large viral double stranded DNA pumps, which are found in all tailed bacteriophages and HERPES viruses. The DNA is actively pumped trough a central cavity formed by 12 subunits that spontaneously assemble to form a spiral-like oligomeric structure. The mechanisms of self-assembly, DNA pumping as well as the energetic of DNA pumping are unknown. The aim of our study is to determine the three dimensional structure of different portal proteins from various bacteriophages and HERPES viruses, both in empty state and in complex with engineered DNA oligonucleotides. In this way we hope to shed light on the mechanisms of DNA pumping, thus providing a useful starting point for the rational drug design of powerful antiviral agents.

Selected Publications

Bhardwaj, A., Walker-Kopp, N., Casjens, S.R., and Cingolani, G. (2009) An evolutionarily conserved family of virion tail needles related to bacteriophage P22 gp26: correlation between structural stability and length of the a-helical trimeric coiled-coil. J. Mol. Biol. In press

Mitrea, D.M., Butler, J.S., Mitrousis, G., Cingolani, G. and Loh, S. N. (2009). Structural and Thermodynamic Analysis of Conformationally-Strained Circular Permutants of Barnase. Biochemistry. 48(15):3497-507.

Koksal, A., Nardozzi, J., and Cingolani, G. (2009) Dimeric quaternary structure of the prototypical dual specificity phosphatase VH1. J. Biol. Chem. 284(15):10129-37.

Olia, S.A., Casjens, S., and Cingolani, G. (2009) Structural Plasticity of the phage P22 tail-needle gp26 probed with Xenon Gas. Protein Science. 18(3):537-548.

Olia, S.A., and Cingolani, G. (2008) A shifty stop for a hairy tail. Mol. Microbiology, 70(3):549-53.

Bhardwaj, A., Walker-Kopp N, Wilkens, S., and Cingolani, G. (2008) Foldon-guided self-assembly of ultra stable protein fibers. Protein Science 17(9):1475-85.

Lorenzen, K., Olia, S.A., Uetrecht, C., Cingolani, G., and Heck, A.J.R. (2008). Determination of stoichiometry and conformational changes in the first step of the P22 tail assembly. J. Mol. Biol. 379(2):385-96.

Mitrousis, G., Olia, S.A., Walker and Cingolani, G. (2008). Molecular basis for the recognition of snurportin 1 by importin b. J. Biol. Chem. 283(12):7877-84.

Zheng, H., Olia, S.A., Hankins, M., Andrews, S., Cingolani, G., and Gonen, T, (2008). A conformational switch in bacteriophage P22 portal protein primes genome injection. Molecular Cell. 29(3), 376-383.

Olia, S.A., Casjens, S. and Cingolani, G. (2007) Structure of Phage P22 Cell Envelope Penetrating Needle. Nature Struc Mol Biol. 14(12), 1221-1226.

Olia, S.A., Bhardwaj, A., Joss, L., Casjens, S., and Cingolani, G. (2007) The role of gene 10 protein in the hierarchical assembly of the bacteriophage P22 portal vertex structure. Biochemistry. 46(30), 8776-8784.

Bhardwaj, A., Olia, S.A., Walker-Kopp N, and Cingolani, G. (2007) Domain organization and polarity of tail needle gp26 in the portal vertex structure of bacteriophage P22. J. Mol. Biol. 371(2), 374-87.

Olia, A., Al-Bassam, J., Winn-Stapley, D.A., Joss, L., Casjens, S., and Cingolani, G. (2006) Binding induced stabilization and oligomerization of portal closure factor gp4 in the assembly pathway of phage P22 tail. J. Mol. Biol. 363, 558-576.

Cingolani, G., Andrews, D., and Casjens, S. (2006) Crystallogenesis of bacteriophage P22 tail accessory factor gp26 at acidic and neutral pH. Acta Cryst. F 62, 477-482.

Taylor, D.J., Speir, J.A., Reddy, V., Cingolani, G., Pringle, F.M., Ball, L.A. and Johnson, J.E. (2006) Preliminary X-ray characterization of authentic providence virus and attempts to express its coat protein gene in recombinant baculovirus. Arch Virol. 151(1):155-65.

Andrews D, Butler JS, Al-Bassam J, Joss L, Winn-Stapley DA, Casjens S, and Cingolani, G. (2005) Bacteriophage P22 Tail Accessory Factor GP26 Is a Long Triple-stranded Coiled-coil.  J. Biol. Chem. 280(7): 5929-33.

Chen MH, Ben-Efraim I, Mitrousis G, Walker-Kopp N, Sims PJ, and Cingolani, G. (2005) Phospholipid scramblase 1 (PLSCR1) contains a non-classical nuclear localization signal with unique binding site in importin a. J. Biol. Chem. 280(11):10599-606.

Tang L., Marion W., Cingolani, G., Prevelige P.E. Jr., and Johnson J.E. (2005) The three-dimensional structure of the tail machine of bacteriophage P22. EMBO J. 24(12):2087-95.

Publications - link to PubMed

This profile was last updated on 05/29/2009

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