Research Groups
Mammalian Biology: Structural and Computational Biology
Research Interests and Description
Staff Research Scientist: Neel Sarovar Bhavesh
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 system are required for understanding
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 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, etc, which makes these of commercial interest 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% 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 detergents membrane
proteins and the role of concentration and other factors on the sample quality.
It could further help in establishing a number of protocols that were successful.
This could also lead to fast screening of drugs.
Recent Publications
Honanappa, S., Gouveia, S.M., Weisbrich, A., Damberger, F.F., Bhavesh, N.S., Jawhari, H., Grigoriev,L., Rijssel, F.J.A.V., Buey, R.M., Lawera, A., Jelesarov, L., Winkler, F.K., Wuthrich, K., Akhmanova, A., Steinmetz, M.O. 2009. An EB1-binding motif acts as a microtubule tip localization signal.Cell 138, 366-376
Bhavesh, N.S., Sinha, R., KrishnaMohan, P.M., Hosur, R.V. 2003. NMR elucidation of early folding hierarchy in HIV-1 protease. J. Biol. Chem. 278, 19980-19985Juneja, J., Bhavesh, N.S., Udgaonkar, J.B., Hosur, R.V. 2002. NMR identification and characterization of the flexible regions in the 160 kDa molten globule-like aggregate of Barstar at low pH. Biochemistry 41, 9885-9899
Juneja, J., Bhavesh, N.S., Udgaonkar, J.B., Hosur, R.V. 2002. NMR identification and characterization of the flexible regions in the 160 kDa molten globule-like aggregate of Barstar at low pH. Biochemistry 41, 9885-9899
