GPCRchimeraDB: A Database of Chimeric G Protein-Coupled Receptors (GPCRs) to Assist Their Design

[Display omitted] •GPCRchimeraDB is a database that collects previously designed chimeric GPCRs.•A chimeric GPCR is obtained by merging 2 natural GPCRs.•Chimeric GPCRs enable to increase understanding in poorly characterized GPCRs.•GPCRchimeraDB describes and visualizes chimeric and natural GPCRs ex...

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Published in:Journal of molecular biology Vol. 437; no. 14; p. 169164
Main Authors: Crauwels, Charlotte, Díaz, Adrián, Vranken, Wim
Format: Journal Article
Language:English
Published: Netherlands Elsevier Ltd 15.07.2025
Subjects:
chimera
class
Databases, Protein
G protein-coupled receptor
GPCR
Humans
hybrid
ligands
molecular biology
protein design
Protein Engineering - methods
Receptors, G-Protein-Coupled - chemistry
Receptors, G-Protein-Coupled - genetics
Receptors, G-Protein-Coupled - metabolism
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Signal Transduction
therapeutics
G protein-coupled receptor
chimera
GPCR
hybrid
protein design
ISSN:0022-2836, 1089-8638, 1089-8638
Online Access:Get full text
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Summary:[Display omitted] •GPCRchimeraDB is a database that collects previously designed chimeric GPCRs.•A chimeric GPCR is obtained by merging 2 natural GPCRs.•Chimeric GPCRs enable to increase understanding in poorly characterized GPCRs.•GPCRchimeraDB describes and visualizes chimeric and natural GPCRs extensively.•Guidelines and tools to support the design of novel chimeric GPCRs are provided. G protein-coupled receptors (GPCRs) are membrane proteins crucial to numerous diseases, yet many remain poorly characterized and untargeted by drugs. Chimeric GPCRs have emerged as valuable tools for elucidating GPCR function by facilitating the identification of signaling pathways, resolving structures, and discovering novel ligands of poorly understood GPCRs. Such chimeric GPCRs are obtained by merging a well- and less-well-characterized GPCR at the intracellular limits of their transmembrane regions or intracellular loops, leveraging knowledge transfer from the well-characterized GPCR. However, despite the engineering of over 200 chimeric GPCRs to date, the design process remains largely trial-and-error and lacks a standardized approach. To address this gap, we introduce GPCRchimeraDB (https://www.bio2byte.be/gpcrchimeradb/), the first comprehensive database dedicated to chimeric GPCRs. It catalogs 212 chimeric receptors, identified through literature review, and includes 1,755 class A natural GPCRs, enabling connections between chimeras and their parent receptors while facilitating the exploration of novel parent combinations. Both chimeric and natural GPCR entries are extensively described at the sequence, structural, and biophysical level through a range of visualization tools, with annotations from resources like UniProt and GPCRdb and predictions from AlphaFold2 and b2btools. Additionally, GPCRchimeraDB offers a GPCR sequence aligner and a feature comparator to investigate differences between natural and chimeric receptors. It also provides design guidelines to support rational chimera engineering. GPCRchimeraDB is therefore a resource to facilitate and optimize the design of new chimeras, so helping to gain insights into poorly characterized receptors and contributing to advances in GPCR therapeutic development.
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ISSN:0022-2836
1089-8638
1089-8638
DOI:10.1016/j.jmb.2025.169164