ArticleNature communications2024
Conformational coupling between extracellular and transmembrane domains modulates holo-adhesion GPCR function.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed.
- Non-canonical cleavage of GPR125/ADGRA3 releases extracellular receptor fragments detectable in cerebrospinal fluid.iScience · 2026Article
- CD97/Cells · 2026Review
- AlloPool is a deep learning framework that infers protein allostery from molecular dynamics simulations.PLoS biology · 2026Article
- Ligand-tuned extracellular domain dynamics are correlated with signaling states in an adhesion GPCR.Science advances · 2026Article
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- The atypical adhesion GPCR ADGRA1 controls hippocampal inhibitory circuit function.Cell reports · 2026Article
- Structural basis of GAIN domain autoproteolysis and cleavage-resistance in the adhesion G-protein coupled receptors.Nature communications · 2026Article
- Cytoplasmic tail diversity determines the effector bias of the adhesion GPCR ADGRL2.Cell chemical biology · 2026Article
- The expanding roles of adhesion GPCRs in neural circuit assembly.Molecules and cells · 2026Review
- From a Shared Stress to Cell-Type-Specific Responses: The Heterogeneous Mechanisms of High Glucose-Induced Cellular Senescence in Diabetic Kidney Disease.Journal of diabetes research · 2026Review
- The far extracellular CUB domain of the adhesion GPCR ADGRG6/GPR126 is a key regulator of receptor signaling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Self-cleavage of the GAIN domain of adhesion G protein-coupled receptors requires multiple domain-extrinsic factors.Nature communications · 2025Article
- Cytoplasmic tail composition modulates the G protein and arrestin-3 signaling bias of the adhesion GPCR LPHN2.bioRxiv : the preprint server for biology · 2025Article
- Structural basis for regulation of CELSR1 by a compact module in its extracellular region.Nature communications · 2025Article
Corrections and comments
- Update of
Authors and funding
9 authors.
Funding
Abstract
Adhesion G Protein-Coupled Receptors (aGPCRs) are key cell-adhesion molecules involved in numerous physiological functions. aGPCRs have large multi-domain extracellular regions (ECRs) containing a conserved GAIN domain that precedes their seven-pass transmembrane domain (7TM). Ligand binding and mechanical force applied on the ECR regulate receptor function. However, how the ECR communicates with the 7TM remains elusive, because the relative orientation and dynamics of the ECR and 7TM within a holoreceptor is unclear. Here, we describe the cryo-EM reconstruction of an aGPCR, Latrophilin3/ADGRL3, and reveal that the GAIN domain adopts a parallel orientation to the transmembrane region and has constrained movement. Single-molecule FRET experiments unveil three slow-exchanging FRET states of the ECR relative to the transmembrane region within the holoreceptor. GAIN-targeted antibodies, and cancer-associated mutations at the GAIN-7TM interface, alter FRET states, cryo-EM conformations, and receptor signaling. Altogether, this data demonstrates conformational and functional coupling between the ECR and 7TM, suggesting an ECR-mediated mechanism for aGPCR activation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.