Featured Research Biological Sciences & Bioengineering

Structure, Function and Novel Signaling Pathways of the "Non-canonical" G
Protein-Coupled Receptor
PI: Prof. Arun K. Shukla

Structural visualization of GPCR signaling termination

G Protein-Coupled Receptors (GPCRs) are the main conduit of information transfer across the cell membrane. These receptors and their signaling networks are intricately involved in almost every physiological and pathophysiological process in human body such as cardiovascular regulation, immune response, neurotransmission, behavior and mood regulation. About half of the currently prescribed drugs target this class of receptors including alpha and beta blockers, angiotensin receptor blockers and anti-histamines. GPCR targeting drugs are used in congestive heart failure, hypertension, asthma, allergies, schizophrenia, Parkinson's disease and cancer. Our goal is to understand the structural basis of activation and signaling of selected non-canonical GPCRs and ultimately, leverage this information to improve therapeutic manipulation in human diseases. We utilize synthetic chaperones generated through combinatorial biology and directed evolution approaches to capture and visualize distinct conformational states of GPCRs and their signaling complexes. Our research projects involve a multifunctional approach including cellular signaling, protein biochemistry, receptor pharmacology and structural biology.

This figure represents the superimposition of a GPCR-G protein complex and a GPCR-arrestin protein complex. The GPCR component is shown in green and the arrestin component is in red. The subunits of the heterotrimeric G proteins are shown in blue (Gα), yellow (Gβ) and magenta (Gγ). This superimposition reflects the overlapping nature of G protein and arrestin binding sites in the GPCRs and therefore, explains the arrestin mediated G protein signaling termination event of GPCRs.




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