Cell signalling
Shared class A GPCR activation path
Open access · cc by · source: Europe PMC
Class A GPCRs share a conserved residue-contact rearrangement pathway from ligand pocket to G-protein site.
Study at a glance
- Design
- Computational / modelling — Residue–residue contact score comparison across inactive and active Class A GPCR structures
- N
- N=169 · 142 inactive and 27 active structures compared
- Population
- Class A GPCR crystal/cryo-EM structures
- Outcome
- Conserved 34-residue-pair activation contact pathway
Structured fields used in claim comparison tables when every cited study has a complete layer.
Key findings
A 34-residue-pair pathway across layers; comparisons used 142 inactive and 27 active structures (p<0.001).
Methodology
Quantified residue–residue contact scores across inactive/active structures and identified conserved switching/repacking contacts.
Limitations
Does not replace ligand-specific pharmacology for every receptor.
How this study connects
Role on claims
Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.
Multiple empirical papers in this library examine cell signalling with mechanistic biological findings.
Evidence for the claim as stated.
A 34-residue-pair pathway across layers; comparisons used 142 inactive and 27 active structures (p<0.001).
Evidence for the claim as stated.
Systems and scales differ across cell signalling studies (species, tissues, methods), so mechanisms should not be over-generalised.
Evidence for the claim as stated.
Class A GPCR activation was inferred from residue–residue contact scores across 142 inactive and 27 active structures (p<0.001), yielding a 34-residue-pair pathway across layers. That is comparative structural biology on deposited structures (often crystallography or cryo-EM of isolated receptors), not a trafficking EM study of endosomes, and it does not replace ligand-specific pharmacology.
Evidence for the claim as stated.
Only the caveolar paper is clearly an ultrastructure-of-a-coat study. GPCR work compares 142 inactive and 27 active deposited structures; APEX2 is proteomics; salmon work is a 30-day transcriptome of fat-cell differentiation; Bt OMV uptake is live light-microscopy trafficking. Calling all five 'electron microscopy papers' overstates shared methods.
Evidence for the claim as stated.
Resolution targets disagree. Caveolar EM asks about coat stoichiometry (Cavin 1 trimers; exclusion of EHD2/pacsin 2). GPCR contact maps ask about conserved switches across receptors (34 residue pairs). OMV live imaging asks about a 15-minute endocytic route. Those answers cannot substitute for one another.
Evidence for the claim as stated.
Open questions
Tensions this paper is part of
From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.
Systems and scales differ across cell signalling studies (species, tissues, methods), so mechanisms should not be over-generalised.
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- Supports · LOX1 oxylipins close stomata in defense
Only the caveolar paper is clearly an ultrastructure-of-a-coat study. GPCR work compares 142 inactive and 27 active deposited structures; APEX2 is proteomics; salmon work is a 30-day transcriptome of fat-cell differentiation; Bt OMV uptake is live light-microscopy trafficking. Calling all five 'electron microscopy papers' overstates shared methods.
- Supports · What proteins build the caveolar coat?
- Supports · Mapping the faces of mitochondria and ER
- Supports · Salmon fat-cell differentiation transcriptome
- Supports · How do gut-bacteria vesicles enter host cells?
Resolution targets disagree. Caveolar EM asks about coat stoichiometry (Cavin 1 trimers; exclusion of EHD2/pacsin 2). GPCR contact maps ask about conserved switches across receptors (34 residue pairs). OMV live imaging asks about a 15-minute endocytic route. Those answers cannot substitute for one another.
- Supports · What proteins build the caveolar coat?
- Supports · How do gut-bacteria vesicles enter host cells?
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