ArticleNature communications2024
A neurodevelopmental disorder mutation locks G proteins in the transitory pre-activated state.
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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 13 papers.
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13citing papers in PubMed
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Who cites it
13 citing papers in PubMed.
- Structural basis for modulation of group III mGlu receptors by transsynaptic interactions.Science advances · 2026Article
- The structure of the dopamine DScience advances · 2026Article
- A Ligand-Triggered Receptor Conformation Enables the Design of Selective Agonists for the Dopamine 3 Receptor (DJACS Au · 2026Article
- G-protein regulatory network governs receptor internalization dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Dopamine D2 Receptor Isoform Heteroreceptor Complexes with the Growth Hormone Secretagogue Receptor 1a Reveals Isoform-Specific Interaction Interface Dynamics.Journal of chemical information and modeling · 2026Article
- Identification of Dopamine D2 Receptor as a Direct Target of Salidroside and Tyrosol by Integrated Transcriptomic and Biophysical Approaches.Pharmaceuticals (Basel, Switzerland) · 2026Article
- NovelGenes & diseases · 2026Article
- Pathogenic Gαo Mutants Drive Dominant GPCR Coupling in GNAO1 Encephalopathies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Deciphering a mechanistic basis for the pathological effect of the GNAO1 E246K variant in neurodevelopmental disorder.BBA advances · 2026Article
- Atypical GNAO1 variants in severe childhood speech disorders: clinical, genetic, and molecular insights.Molecular autism · 2025Article
- Structural insights into endogenous agonist selectivity of aminergic receptors from the octopamine βPNAS nexus · 2025Article
- Dominant Gα mutations in human disease: unifying mechanisms and treatment strategies.EMBO molecular medicine · 2025Review
- Identification of a Lipid-Exposed Extrahelical Binding Site for Positive Allosteric Modulators of the Dopamine DACS chemical neuroscience · 2025Article
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Authors and funding
20 authors.
Kevin M Knight *Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0002-0299-6476
Brian E Krumm *Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0001-6039-4767
Nicholas J KapolkaDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
W Grant LudlamDepartment of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, University of Florida, Jupiter, FL, USA.ORCID 0000-0002-2701-8791
Meng CuiDepartment of Pharmaceutical Sciences Northeastern University, Boston, MA, USA.ORCID 0000-0002-3895-135X
Sepehr ManiDepartment of Pharmaceutical Sciences Northeastern University, Boston, MA, USA.ORCID 0009-0003-5487-4723
Iya PrytkovaNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Elizabeth G ObarowDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Tyler J LefevreDepartment of Pharmacology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-7665-3353
Wenyuan WeiDepartment of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, USA.ORCID 0009-0008-5146-8048
Ning MaDepartment of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, USA.ORCID 0000-0003-4653-7797
Xi-Ping HuangDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0002-2585-653X
Jonathan F FayDepartment of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Baltimore, MD, USA.ORCID 0000-0003-1822-2384
Nagarajan VaidehiDepartment of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, USA.ORCID 0000-0001-8100-8132
Alan V SmrckaDepartment of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
Paul A SlesingerNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-3868-7528
Diomedes E LogothetisDepartment of Pharmaceutical Sciences Northeastern University, Boston, MA, USA.ORCID 0000-0002-0576-884X
Kirill A MartemyanovDepartment of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, University of Florida, Jupiter, FL, USA.ORCID 0000-0002-9925-7599
Bryan L RothDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0002-0561-6520
Henrik G DohlmanDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. hdohlman@med.unc.edu.ORCID 0000-0003-2443-0729
Funding
Subject CollectionU10AA008401 · NIAAA · SUNY DOWNSTATE MEDICAL CENTER · PI JAY Arnold TISCHFIELD · 1989 to 2026
$162.7MStructural Determinants of PIP2 RegulationR01HL059949 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Leigh Daniel Plant · 1998 to 2026
$11.6MGENETIC EPIDEMIOLOGY OF AGING IN UTAH PEDIGREESR01AG018734 · NIA · UNIVERSITY OF UTAH · PI HUNT, STEVEN C. · 2000 to 2007
$7.5MNegative and positive feedback in cell signalingR35GM118105 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Henrik G. Dohlman · 2016 to 2026
$6.6MStructural Analysis of Alcohol-dependent Activation of GIRKsR01AA018734 · NIAAA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Paul A Slesinger · 2010 to 2026
$6.6MRegulation of Striatal Signaling by RGS ProteinsR01DA036596 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Kirill A. Martemyanov · 2014 to 2026
$6.5MMolecular Details of Psychoactive Drug ActionsR01MH112205 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Bryan L. Roth, Brian K Shoichet · 2017 to 2026
$6.1MUnderstanding and Manipulating Phospholipase C and G Protein beta gamma subunit Signaling NetworksR35GM127303 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alan V. Smrcka · 2018 to 2026
$4.8MStructural dynamics underlying GPCR-G protein selectivityR01GM117923 · NIGMS · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI VAIDEHI, NAGARAJAN · 2017 to 2024
$3.8MSTRUCTURE AND FUNCTION OF MRG-FAMILY RECEPTORSR01DA055656 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Bryan L. Roth, Brian K Shoichet · 2022 to 2026
$2.8MAn integrated toolkit combining computational systems biology techniques with molecular dynamics simulations to delineate functionality of GPCRsR01LM013876 · NLM · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI RODIN, ANDREI, VAIDEHI, NAGARAJAN · 2022 to 2025
$1.5MElucidating transsynaptic regulation of metabotropic glutamate receptorsF32NS124758 · NINDS · UNIVERSITY OF FLORIDA · PI LUDLAM, WILLIAM GRANT · 2022 to 2025
$216kNHLBI NIH HHS R01 HL059949NIAAA NIH HHS F31 AA027949NIAAA NIH HHS R01 AA018734NIAAA NIH HHS U10 AA008401NIDA NIH HHS R01 DA036596NIDA NIH HHS R01 DA055656NIGMS NIH HHS R01 GM117923NIGMS NIH HHS R35 GM118105NIGMS NIH HHS R35 GM127303NIMH NIH HHS R01 MH112205NINDS NIH HHS F32 NS124758NLM NIH HHS R01 LM013876U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL059949U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01GM117923U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM118105U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM127303U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH112205U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) F32NS124758U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) F31AA027949U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) R01AA018734U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) U10AA008401U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) RO1DA036596U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM) R01LM013876
Abstract
Many neurotransmitter receptors activate G proteins through exchange of GDP for GTP. The intermediate nucleotide-free state has eluded characterization, due largely to its inherent instability. Here we characterize a G protein variant associated with a rare neurological disorder in humans. Gα
Indexed as
Cryoelectron MicroscopyGuanosine DiphosphateGuanosine TriphosphateMutationGTP-Binding Protein alpha Subunits, Gi-GoGTP-Binding Protein gamma SubunitsGTP-Binding ProteinsHEK293 CellsHumansNeurodevelopmental DisordersProtein BindingReceptors, Dopamine D2GTP-Binding Protein alpha Subunits, Gi-GoGTP-Binding Protein gamma SubunitsGTP-Binding ProteinsGuanosine DiphosphateGuanosine TriphosphateReceptors, Dopamine D2
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