ArticleProceedings of the National Academy of Sciences of the United States of America2006
Structural and dynamical changes in an alpha-subunit of a heterotrimeric G protein along the activation pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- Article
- Conformational Heterogeneity Underlying Divergent Signaling in Class A G Protein-Coupled Receptors.ACS pharmacology & translational science · 2025Review
- G Protein Activation Occurs via a Largely Universal Mechanism.The journal of physical chemistry. B · 2024Article
- G-Protein Phosphorylation: Aspects of Binding Specificity and Function in the Plant Kingdom.International journal of molecular sciences · 2022Review
- DEER Analysis of GPCR Conformational Heterogeneity.Biomolecules · 2021Review
- Capturing Peptide-GPCR Interactions and Their Dynamics.Molecules (Basel, Switzerland) · 2020Review
- Structures of the Rhodopsin-Transducin Complex: Insights into G-Protein Activation.Molecular cell · 2019Article
- Conformational plasticity of the intracellular cavity of GPCR-G-protein complexes leads to G-protein promiscuity and selectivity.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Development of an antibody fragment that stabilizes GPCR/G-protein complexes.Nature communications · 2018Article
- GProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses.Nature communications · 2017Article
- Article
- Nanosecond Dynamics of Gαi1 Bound to Nucleotides or Ric-8A, a Gα Chaperone with GEF Activity.Biophysical journal · 2016Article
- Structural Elements in the Gαs and Gαq C Termini That Mediate Selective G Protein-coupled Receptor (GPCR) Signaling.The Journal of biological chemistry · 2016Article
- Invited review: Activation of G proteins by GTP and the mechanism of Gα-catalyzed GTP hydrolysis.Biopolymers · 2016Review
- Conformational dynamics of a G-protein α subunit is tightly regulated by nucleotide binding.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Computational Simulation of the Activation Cycle of Gα Subunit in the G Protein Cycle Using an Elastic Network Model.PloS one · 2016Article
- A positive genotype-phenotype correlation in a large cohort of patients with Pseudohypoparathyroidism Type Ia and Pseudo-pseudohypoparathyroidism and 33 newly identified mutations in the GNAS gene.Molecular genetics & genomic medicine · 2015Article
- The guanine nucleotide exchange factor Ric-8A induces domain separation and Ras domain plasticity in Gαi1.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- A GTPase chimera illustrates an uncoupled nucleotide affinity and release rate, providing insight into the activation mechanism.Biophysical journal · 2014Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Galpha subunits of heterotrimeric G proteins (Galphabetagamma) mediate signal transduction via activation by receptors and subsequent interaction with downstream effectors. Crystal structures indicate that conformational changes in "switch" sequences of Galpha, controlled by the identity of the bound nucleotide (GDP and GTP), modulate binding affinities to the Gbetagamma subunits, receptor, and effector proteins. To investigate the solution structure and dynamics of Galphai1 through the G protein cycle, nitroxide side chains (R1) were introduced at sites in switch II and at a site in helix alpha4, a putative effector binding region. In the inactive Galphai1(GDP) state, the EPR spectra are compatible with conformational polymorphism in switch II. Upon complex formation with Gbetagamma, motions of R1 are highly constrained, reflecting direct contact interactions at the Galphai1-Gbeta interface; remarkably, the presence of R1 at the sites investigated does not substantially affect the binding affinity. Complex formation between the heterotrimer and activated rhodopsin leads to a dramatic change in R1 motion at residue 217 in the receptor-binding alpha2/beta4 loop and smaller allosteric changes at the Galphai1-Gbetagamma interface distant from the receptor binding surface. Upon addition of GTPgammaS, the activated Galphai1(GTP) subunit dissociates from the complex, and switch II is transformed to a unique conformation similar to that in crystal structures but with a flexible backbone. A previously unreported activation-dependent change in alpha4, distant from the interaction surface, supports a role for this helix in effector binding.
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