Research Groups
Mammalian Biology: Structural and Computational Biology
Research Interests and Description
Staff Research Scientist: Neel Sarovar Bhavesh, PhD
Group Leader: Amit Sharma
Group Members
Research Interests
Protein structure, function and crystallography.Description of Research
In solution (NMR) structural studies
Genomic data suggest that about 20-30% of genome codes for Intrinsically Unstructured Proteins (IUP). In most cases a flexible state is necessary for their function and regulation.
Therefore, structural and dynamical studies of such systems are required to understand their function. NMR spectroscopy, in addition to normal application for 3D structure determination of folded proteins, is unparalleled in its ability to provide atomic resolution of structural and dynamical information of unfolded and flexible proteins and their complexes. We use the latest multidimensional NMR methods for atomic resolution characterization of IUPs and their complexes. Computational analyses of various genomes have typically predicted that 20-25% of a proteome consists of membrane proteins.
The vital roles of membrane proteins in biological systems include ion/molecule transport, virus reception, energy regulation, signaling, and so forth, which renders these commercially interesting as targets for drug development. An initial challenge is thus to determine atomic resolution structures and study their function and dynamics. The challenges involved in structure determination become clear when considering the Protein Data Bank (PDB), which contains only 0.3% of integral membrane protein structures.
For the preparation of a suitable NMR sample, several steps have to be performed; typically cloning, over-expression, purification and extraction/refolding. Each of these steps can be difficult or even problematic for a given protein. We are selecting interesting outer membrane protein candidates and have chosen a screening approach for the selection of a suitable reconstitution method. Besides providing a possible structure, this approach is likely to shed light on the interaction of different, detergent membrane proteins and the role of concentration and other factors on the sample quality.
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Figure 1: An electrostatics surface view of ETR3-RRM3 bound to GGU-GUG RNA in the RRM3-RNA complex.
Figure 2: Comparison of structures of ETR3-RRM3 free and bound to RNA.
Recent Publications
Kashyap, M., Jagga, Z., Das, B.K., Arockiasamy, A., Bhavesh, N.S. 2011. 1H, 13C and 15N NMR assignments of inactive form of P1 endolysin Lyz Biomol. NMR Assign In press PubMed link
Munshi, S.U., Taneja, S., Bhavesh, N.S., Shastri, J., Aggarwal, R. Jameel, S. 2011. Metabonomic analysis of hepatitis E patients shows deregulated metabolic cycles and abnormalities in amino acid metabolism. J Viral Hepat In press PubMed link
Bhatt, H., Kashyap, M., Bhavesh, N.S. 2010. 1H, 13C and 15N NMR assignments of RNA recognizing motifs 1 and 2 of BRUNOL-3 protein from human involved in myotonic dystrophy. Biomol NMR Assign 4, 143-145 PubMed link
De Groot, C., Jelesarov, I., Damberger, F.F., Bjelic, S., Schärer, M.A., Bhavesh, N.S., Grigoriev, I., Buey, R.M., Wüthrich, K., Capitani, G., Akhmanova, A. Steinmetz, M.O. 2010. Molecular insights into mammalian end-binding protein heterodimerization. J Biol Chem 285, 5802-5814 PubMed link
Mandal, P.K., Bhavesh, N.S., Chauhan, V.S. Fodale, V. 2010. NMR investigations of Aβ peptide interactions with propofol at clinically relevant concentrations with and without aqueous halothane solution. J Alzheimers Dis 21, 1303-1309 PubMed link
Honnappa, S., Montenegro-Gouveia, S., Weisbrich, A., Damberger, F.F., Bhavesh, N.S., Jawhari, H., Grigoriev, I., van Rijssel, F.J.A., Buey, R.M., Lawera, A., Jelesarov, I., Winkler, F.K., Wüthrich, K., Akhmanova, A., Steinmetz, M.O. 2009. A universal EB1-binding motif acts as a microtubule tip localization signal. Cell 138, 366-376 PubMed link
