ArticleProceedings of the National Academy of Sciences of the United States of America2009
Identification of two distinct inactive conformations of the beta2-adrenergic receptor reconciles structural and biochemical observations.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 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
147 citing papers in PubMed.
- Trial
- A Minimalist Model for Navigating Conformational Landscape Uncovers the Activation Mechanism of βACS physical chemistry Au · 2026Article
- Agonist Binding Reshapes the Kinetic Landscape and Allosteric Communication of APLNR Toward Activation-Competent States.International journal of molecular sciences · 2026Article
- Benchmarking AI Protein Structure Predictors Reveals a Persistent Bias in Multi-State Proteins.bioRxiv : the preprint server for biology · 2026Article
- From possibility to precision in macromolecular ensemble prediction.Nature methods · 2026Review
- Investigating the electrostatics underlying activation of the βBiochimica et biophysica acta. Biomembranes · 2026Article
- Temporally resolved and interpretable machine learning model of GPCR conformational transition.Nature communications · 2025Article
- Conformational Heterogeneity Underlying Divergent Signaling in Class A G Protein-Coupled Receptors.ACS pharmacology & translational science · 2025Review
- Structure and dynamics determine G protein coupling specificity at a class A GPCR.Science advances · 2025Article
- Mechanistic insights into G-protein coupling with an agonist-bound G-protein-coupled receptor.Nature structural & molecular biology · 2024Article
- IDRWalker: A Random Walk Based Tool for Generating Intrinsically Disordered Regions in Large Protein Complexes.ACS omega · 2024Article
- Cellular lipids regulate the conformational ensembles of the disordered intracellular loop 3 in β2-adrenergic receptor.iScience · 2024Article
- Article
- Article
- Structures of Adrenoceptors.Handbook of experimental pharmacology · 2024Review
- Elucidation of the structural basis for ligand binding and translocation in conserved insect odorant receptor co-receptors.Nature communications · 2023Article
- Cellular Lipids Regulate the Conformational Ensembles of the Disordered Intracellular Loop 3 in β2 Adrenergic Receptor.bioRxiv : the preprint server for biology · 2023Article
- Article
- The dynamics of agonist-βNature chemistry · 2023Article
- Activity Map and Transition Pathways of G Protein-Coupled Receptor Revealed by Machine Learning.Journal of chemical information and modeling · 2023Article
87 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fully understanding the mechanisms of signaling proteins such as G protein-coupled receptors (GPCRs) will require the characterization of their conformational states and the pathways connecting those states. The recent crystal structures of the beta(2)- and beta(1)-adrenergic receptors in a nominally inactive state constituted a major advance toward this goal, but also raised new questions. Although earlier biochemical observations had suggested that these receptors possessed a set of contacts between helices 3 and 6, known as the ionic lock, which was believed to form a molecular switch for receptor activation, the crystal structures lacked these contacts. The unexpectedly broken ionic lock has raised questions about the true conformation(s) of the inactive state and the role of the ionic lock in receptor activation and signaling. To address these questions, we performed microsecond-timescale molecular dynamics simulations of the beta(2)-adrenergic receptor (beta(2)AR) in multiple wild-type and mutant forms. In wild-type simulations, the ionic lock formed reproducibly, bringing the intracellular ends of helices 3 and 6 together to adopt a conformation similar to that found in inactive rhodopsin. Our results suggest that inactive beta(2)AR exists in equilibrium between conformations with the lock formed and the lock broken, whether or not the cocrystallized ligand is present. These findings, along with the formation of several secondary structural elements in the beta(2)AR loops during our simulations, may provide a more comprehensive picture of the inactive state of the beta-adrenergic receptors, reconciling the crystal structures with biochemical studies.
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.