The Rockefeller University, Box 187
1230 York Avenue
New York, NY 10065

Telephone: 212-327-8284
Fax: 212-327-7904

nkapoor@mail.rockefeller.edu

Curriculum Vitae

Education:

Ph.D. in Biochemistry and Molecular Biology, Rockefeller University 2004-present
M.Sc. in Chemistry, Indian Institute of Technology, Kanpur 1999-2004

Research:


Understanding the mechanism of Heterotrimeric G-protein activation
Heptahelical G protein-coupled receptors (GPCRs) couple to heterotrimeric G proteins to relay extracellular signals to intracellular signaling networks, but the molecular mechanism underlying GDP release by the G protein α-subunit is not well understood. The signal of activation is delivered to the G protein pocket via a5 helix, a microdomain on Ga protein which allosterically couples the conformational change necessary for nucleotide exchange to receptor activation. A number of theoretical as well as experimental models are available that explain various aspects of this process but still the overall understanding of the activation process is incomplete. We have utilized both structural biology and Spectroscopic methods to address this question by studying single amino acid point mutants of a5 helix residues with multifold increased rates of basal nucleotide exchange. Using X-ray crystallography we have been able to trap an intermediate along the activation pathway which has led us to propose a “sequential-release” mechanism for the activation of Heterotrimeric G proteins.  

Mechanistic understanding of the modulatory effect of Calnuc, a novel Ca2+ binding protein towards G protein activation
Calnuc is a novel golgi-resident Ca2+ binding protein that has been shown to interact with the a5 helix of Ga proteins. Since it is well established that a5 helix delivers the receptor mediated activation signal to the catalytic pocket to facilitate nucleotide exchange, we are very much interested in understanding the functional relevance of this interaction. We have established heterologous expression system for both Calnuc and Gai1. Our analysis shows the interaction is dependent both on the Ca2+ bound state of Calnuc and the specific nucleotide bound state of G protein. The exact in vitro functional relevance of this selective interaction is under investigation. We also wish to understand the exact molecular determinants of this interaction and the physiological relevance of the regulation.



Investigation of the Anti-amyloidogenic properties of Calnuc
Calnuc, a novel Ca2+ binding protein has been shown to be substantially upregulated in brains of patients suffering from Alzheimer’s disease (AD). It has also been shown that Calnuc can interact with the Amyloid Precursor Protein (APP), the transmembrane protein whose proteolytic product Ab42 is implicated in the pathology of AD. We are interested in investigating the functional efficacy of Calnuc towards inhibting the aggregation of Ab42 into fibrils and towards dissociation of preformed fibrils both in an in vitro and in vivo setup. We also wish to extend the work to other amyloidogenic peptides like hIAPP, implicated in Type-2 diabetes mellitus.

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Awards:

Published Papers:

1).
Kapoor, N., Menon, S.T., Chauhan, R., Sachdev, P. & Sakmar, T.P.
Structural Evidence for a Sequential Release Mechanism for Heterotrimeric G protein activation
Journal of Molecular Biology,2009, In Press

[not indexed on PUBMED]

Recent Presentations:

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Posters:

1).
Heterotrimeric G-Proteins
Rockefeller University Chemical Biology retreat, May 19-21, 2009