Profile
Our group uses an interdisciplinary approach encompassing a wide array of biophysical, biochemical, and molecular biology techniques for understanding the structure and function of macromolecules with a special thrust on the molecular mechanism of Protein-RNA interactions. Liquid-state NMR spectroscopy and X-ray crystallography are synergistically used in his group for the determination of atomic resolution structures of protein-RNA complexes that provide a wealth of information pertaining to the binding interfaces, recognition mechanisms, and the forces that stabilize these complexes. Current research focuses on RNA binding proteins that are involved in post-transcription regulation of mRNA to decipher a possible general code of RNA recognition. He also uses NMR spectroscopy for metabolic profiling of bio-fluids to understand dysregulation during disease conditions and help in the identification of biomarkers.
Current Focus Areas
Nascent mRNAs undergo extensive chemical modification to produce mature mRNAs before translation. Although the canonical structure of the RRM is generally quite well conserved and restricted, this domain can readily have subtle structural adaptations and is able to recognize a wide spectrum of different RNA and DNA sequences and shapes.
We use NMR for metabolomics, which has the advantages of being non-destructive, quantitative, robust, and highly reproducible. It provides detailed information on molecular structures based on atom-centered nuclear interactions and properties. It detects a wide range of structurally diverse metabolites, providing a metabolic ‘snapshot’ at a particular time point.
Selected Publications
Aggarwal, P. and Bhavesh, N.S. 2021. Hinge like domain motion facilitates human RBMS1 protein binding to proto-oncogene c-myc promoter. Nucleic Acids Res. 49, 5943-5955. DOI: 10.1093/nar/gkab363
Kumari, P. and Bhavesh, N.S. 2021. Human DND1-RRM2 forms a non-canonical domain swapped dimer. Protein Sci. 30, 1184-1195. DOI: 10.1002/pro.4083
Pandey, N.K., Verma, G., Kushwaha, G.S., Suar, M. and Bhavesh, N.S. 2020. Crystal structure of the usher chaperone YadV reveals a monomer with the proline lock in closed conformation suggestive of an intermediate state. FEBS. Lett. 594, 3057-3066. DOI: 10.1002/1873-3468.13883
Bhatt, H., Ganguly, A.K., Sharma, S., Kushwaha, G.S., Khan, M.F., Sen, S. and Bhavesh, N.S. 2020. Structure of an unfolding intermediate of an RRM domain of ETR-3 reveals its native-like fold. Biophys. J. 118, 352-365. DOI: 10.1016/j.bpj.2019.11.3392
Ganguly, A.K., Verma, G., Bhavesh, N.S. 2019. The N-terminal RNA recognition motif of PfSR1 confers semi-specificity for pyrimidines during RNA recognition J. Mol. Biol. 431, 498-510. DOI: 10.1016/j.jmb.2018.11.020