Life Sciences & Biotechnology
Title : | Effect of membrane composition on the organization and dynamics of TM4 helix of class A GPCRs: Functional Implications |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Lipika Mirdha, sambalpur University, Odisha |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | lipikamirdha93@gmail.com |
Equipments : | -20 ºC Refrigerator
Digital Weighing Machine
Extruder set with Holder/Heating Block
Probe sonicator |
Details
Executive Summary : | G protein-coupled receptors (GPCRs) are the largest family of membrane protein receptors, with seven α-helices transmembrane (7TM) domains across the membrane. Ligands bind to these domains in class A GPCRs, and in class B, C, and F GPCRs, they bind to extracellular domains or replace them. The transmembrane domain dynamics play a crucial role in signal transduction across the cell to intracellular binding partners like G-proteins or arrestin. The membrane environment directly or indirectly influences GPCRs' activity, with specific interactions being important for allosteric modulation and stability. For instance, interactions between TM domain and cholesterol have been demonstrated in certain class A GPCRs, which are believed to be important for GPCR activation. However, the effect of membrane physical properties on GPCR dynamics and activity is not well studied. A highly conserved tryptophan residue is present in TM4 among GPCRs classes A, B, and F, but its common role across multiple classes is yet to be established. Tryptophan interacts with residues in TM3 and TM5 for several class A GPCRs, stabilizing agonist binding. However, the crystal structure of class A GPCRs suggests that tryptophan is not located at the ligand binding site, suggesting mutational effects may be indirect. This proposal aims to understand the behavior of transmembrane domains in a membrane environment using template peptides derived from the amino acid sequence of native proteins and evaluate the effect of lipid composition on the interaction between transmembrane helices of class A GPCRs. |
Total Budget (INR): | 40,31,808 |
Organizations involved