DESCRIPTION OF LAB RESEARCH WORK
Structure and dynamics of prokaryotic ligand gated ion channel GLIC and ELIC
Pentameric ligand gated ion channels are responsible for the fast synaptic transmission. It's responsible for various biological functionalities. Loss of function of these channels lead to several neurological disorders. These ion channels interchange among various functional states with major states called resting state, open state and desensitized state. Despite a substantial understanding of the physiological and pathophysiological role of multiple states, there is very little structural information available on these states in physiologically relevant environment. The functions of these channels are heavily modulated by membrane lipids and the mechanism of modulation is still illusive. Therefore, the goal of our lab is to understand the gating phenomenon at the atomic level. We are focusing on the prokaryotic ligand gated ion channels GLIC and ELIC. We employ multidisciplinary biochemical and biophysical techniques such as Cryo-EM, EPR spectroscopy, and Two Electrode Voltage Clamping (TEVC) to elucidate the mechanism of channel functions at the atomic level.Understanding the molecular mechanism of Insect olfactory receptors
Insects such as mosquitoes, ticks, and flies harbour infectious agents and spread deadly diseases like malaria, dengue, yellow fever etc. Dengue is a mosquito borne viral infection and transmitted mainly by Aedes aegypti mosquitoes. Severe dengue leads to serious illness and causes death. This disease prevails mostly in tropical and sub-tropical countries like Latin America and southeast Asia including Singapore. Unfortunately, there is no specific treatment for dengue. Therefore, our current study focused mainly on targeting the host mosquitoes. Insects use olfactory receptors (ORs) to sense the smell which is critical for their survival. Therefore, the olfactory receptor could be targeted to develop newer and most effective repellents or insecticides. In our lab we are using multidisciplinary structural biological and functional techniques to elucidate a clear understanding of the molecular mechanism of insect olfaction by studying on model insect Drosophila.
- Structure and dynamics of prokaryotic ligand gated ion channel GLIC
- Understanding the molecular mechanism of Drosophila olfactory receptors
- Understanding the molecular mechanism of odorant receptor co-receptor (orco) in Anopheles gambiae
10. Basak, S., Kumar, A., Ramsey, S., Gibbs, E., Kapoor, A., Filizola, M. and Chakrapani, S*. (2020) High-resolution Structures of multiple 5-HT3AR-setron complexes reveal a novel mechanism of competitive inhibition. eLife. 9:e57870.
9. Kumar, A., Basak, S., Rao, S., Gicheru, Y., Mayer, M. L., Sansom, M., and Chakrapani, S*. (2020) Mechanism of activation and inhibition of full-length Glycine receptor in membranes. Nature communications. 11, 3752.
8. Basak, S., Gicheru, Y., Kapoor, Abhijeet., Mayer, M. L., Filizola, M. and Chakrapani, S*. (2019) Molecular mechanism of setron-mediated inhibition of full-length 5-HT3A receptor. Nature communications. 10 (1), 3225.
7. Basak, S., Gicheru, Y., Rao, S., Sansom, M. and Chakrapnai, S*. (2018) Cryo-EM reveals two distinct states along serotonin-mediated activation pathway of the full-length 5-HT3A receptor. Nature. 563, 270.
6. Basak, S., Gicheru, Y., Samanta, A., Molugu, S., Huang, W., Fuente, M. D. L., Hughes, T., Taylor, D., Nieman, M., Moiseenkova-Bell, V.Y. and Chakrapani, S*. (2018) Cryo-EM structure of 5-HT3A receptor in its resting conformation. Nature communications. 9, 514.
5. Basak, S., Schmandt, N., Gicheru, Y. and Chakrapani, S*. (2017) Crystal structure and dynamics of a lipid-induced potential desensitized-state of a pentameric ligand-gated channel. eLife. 6:e23886.
4. Balakrishna, A. M., Basak, S., Manimekalai, M. S. S. and Grüber, G*. (2015) Crystal structure of subunits D and F in complex give insight into energy transmission of the eukaryotic V-ATPase from Saccharomyces cerevisiae. Journal of Biological Chemistry. 290, 3183-3196.
3. Basak, S., Lim, J., Manimekalai, M. S. S., Balakrishna, A. M. and Grüber, G*. (2013) Crystal- and NMR structures give insights into the role and dynamics of subunit F of the eukaryotic V-ATPase from Saccharomyces cerevisiae. Journal of Biological Chemistry. 288, 11930-11939.
2. Basak, S., Gayen, S., Ramalingam, J., Grüber, A., Preiser, R. P. and Grüber, G*. (2011) NMR solution structure of NBD94483-502 of the nucleotide binding domain of the Plasmodium yoelii reticulocyte binding protein Py235. FEMS Microbiology Letters. 318, 152-158.
1. Basak, S., Gayen, S., Thaker, Y. R., Manimekalai, M. S. S., Roessle, M., Hunke, C. and Grüber, G*. (2011) Solution structure of subunit F (Vma7p) of the eukaryotic V1VO ATPase from Saccharomyces cerevisiae derived from SAXS and NMR spectroscopy. Biochimica Biophysica Acta-Biomembranes.1808, 360-368.