Shared class A GPCR activation path
Class A GPCRs share a conserved residue-contact rearrangement pathway from ligand pocket to G-protein site.
Source
Common activation mechanism of class A GPCRs
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.
Inspect source passages
Shared class A GPCR activation path
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
34 residue pairs in the pathway.
The pathway is comprised of 34 residue pairs (formed by 35 residues) with conserved rearrangement of residue contacts
142 inactive and 27 active structures compared.
family-wide comparison of the RRCS for the 142 inactive and 27 active state structures shows a statistically significant difference (p<0.001; two sample t -test).
What they did
Quantified residue–residue contact scores across inactive/active structures and identified conserved switching/repacking contacts.
What they found
A 34-residue-pair pathway across layers; comparisons used 142 inactive and 27 active structures (p<0.001).
The limits
What it doesn't show
Does not replace ligand-specific pharmacology for every receptor.
Key terms
- GPCR
- G protein–coupled receptor.
- Class A
- Largest rhodopsin-like GPCR family.
- RRCS
- Residue–residue contact score.
- Transmission switch
- Conserved contact set linking pocket to core.
- Microswitch
- Local motif rewiring during activation.
- Active vs inactive
- Conformational states relative to G-protein coupling.
Flashcards
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Research intelligence for this paper
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Quiz yourself
Residue pairs:
Common questions
Pathway size?
34 residue pairs (35 residues).
Inactive structures?
142.
Active structures?
27.
First common step?
Transmission switch + Na⁺ pocket changes.
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