Areas of Interest
Structure and function of membrane proteins, Ligand gated ion channels.
Structure and function of neurotransmitter receptors
Communication between nerve cells serves as the basis of all brain activity, and one of the fundamental steps involved in signal transmission between the nerve cells, is the conversion of a “chemical” signal liberated at the end of one nerve cell, into an “electrical” signal at the second nerve cell. This step is mediated by a class of membrane bound proteins known as neurotransmitter receptors. Glutamate receptors belong to this family of proteins, and are the main excitatory receptors in the central nervous system.
Our laboratory is interested in gaining an understanding of agonist mediated activation and desensitization of this receptor by determining the structural changes in the protein induced by agonist binding. This is achieved by using various cutting edge spectroscopic methods that allow the characterization of the dynamic state structure of the proteins at a significantly higher resolution than X-ray structures. The structural changes thus determined are correlated to the functional consequences as measured by electrophysiological measurements. These investigations provide a detailed understanding of the agonist controlled function of the glutamate receptors and hence aid in the rational design of drugs targeting this group of important proteins that are involved in diverse neuropathologies, such as epilepsy and ischemia.
Chemical interactions, dynamics and function
- Activity Dependent Inhibition of AMPA Receptors by Zn2+. Carrillo E., Bhatia K., Akimzhanov, A.M., and Jayaraman V., J Neuroscience 2020. 40(45):8629-8636.
- Conformational Spread and Dynamics in Allostery of NMDA Receptors. Durham R.J., Paudyal, N., Carrillo E, Bhatia, N. K., MacLean D.M., Berka V, Dolino D. M., Gorfe, A. A., and Jayaraman V., Proc Natl Acad Sci U S A, 2020 117 (7) 3839-3847.
- Mapping the Conformational Landscape of Glutamate Receptors Using Single Molecule FRET. MacLean DM, Durham RJ, Jayaraman V., Trends Neurosci. 2018. Oct 29 pii: S0166-2236(18)30274-1. doi: 10. 1016/j.tins. 2018. 10.003 [Epub ahead of print] Review (PMID: 30385052)
- The Structure-Energy Landscape of NMDA Receptor Gating. Dolino DM, Chatterjee S, MacLean DM, Flatebo C, Bishop LDC, Shaikh SA, Landes CF, Jayaraman V.
Nat Chem Biol. 2017. Dec; 13(12):1232-1238. doi: 10.1038/nchembio 2487. Epub 2017 Oct 9. (PMID: 28991238)
- Deactivation Kinetics of Acid-Sensing Ion Channel 1a are Strongly pH-Sensitive.
MacLean DM, Jayaraman V. Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):E2504-E2513. doi: 10.1073/pnas.1620508114. Epub 2017 Mar 6. PMID:28265090
Education and Training
Indian Institute of Technology
Graduate Program Affiliations
Biochemistry and Cell Biology