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G Protein-coupled Receptors

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...

Transducer Mechanism: G Protein–Coupled Receptors

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G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...

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Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web

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GPCRana: A web server for quantitative analysis of GPCR structures.

Yu Guo¹, Qingtong Zhou², Bin Wei³

¹iHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China; Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai 200031, China.

Structure (London, England : 1993)

|July 1, 2023

Summary

GPCRana is a new web server for analyzing G protein-coupled receptor (GPCR) structures. It offers user-friendly tools for residue-residue contact score (RRCS) analysis, ligand interactions, and pathway analysis.

Keywords:

GPCR GPCR activation protein-ligand interactions residue-residue contact score structure analysis web server

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Last Updated: Jul 24, 2025

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Area of Science:

Structural Biology
Computational Chemistry
Pharmacology

Background:

G protein-coupled receptors (GPCRs) are crucial drug targets with over 900 known structures.
Existing tools for GPCR structural analysis lack user-friendliness.
Residue-residue contact score (RRCS) provides quantitative insights into GPCR structures.

Purpose of the Study:

To develop GPCRana, a user-friendly web server for comprehensive GPCR structure analysis.
To facilitate the study of GPCR functionality, pharmacology, and conformational changes.
To enable analysis of GPCR structures, including AlphaFold2-predicted models.

Main Methods:

Development of the GPCRana web server with a user-friendly interface.
Implementation of RRCS calculations for all residue pairs with 3D visualization.
Analysis of ligand-receptor interactions, activation pathways, and transmembrane helix movements (RRCS_TMs).
Capability to compare conformational changes between two structures.

Main Results:

GPCRana provides immediate, comprehensive reports on uploaded GPCR structures.
The server visualizes RRCS, ligand-receptor interactions, activation pathways, and helix movements.
Analysis of AlphaFold2 models using GPCRana revealed distinct inter-helical packing.
Conformational changes between structures can be effectively analyzed.

Conclusions:

GPCRana offers a fast, precise, and accessible platform for GPCR structural analysis.
The web server aids in understanding GPCRs' structure-function relationships and pharmacology.
GPCRana is a valuable resource for researchers studying GPCRs, including predicted models.