ArticleBiochemistry2009
Helix dipole movement and conformational variability contribute to allosteric GDP release in Galphai subunits.
Article in Biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Dipoles affect conformational equilibrium.Journal of photochemistry and photobiology. A, Chemistry · 2025Article
- Recent advances in computational studies of GPCR-G protein interactions.Advances in protein chemistry and structural biology · 2019Review
- Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses.Nature communications · 2017Article
- Dynamic Coupling and Allosteric Networks in the α Subunit of Heterotrimeric G Proteins.The Journal of biological chemistry · 2016Article
- Computational Simulation of the Activation Cycle of Gα Subunit in the G Protein Cycle Using an Elastic Network Model.PloS one · 2016Article
- A conserved phenylalanine as a relay between the α5 helix and the GDP binding region of heterotrimeric Gi protein α subunit.The Journal of biological chemistry · 2014Article
- A transient interaction between the phosphate binding loop and switch I contributes to the allosteric network between receptor and nucleotide in Gαi1.The Journal of biological chemistry · 2014Article
- Energetic analysis of the rhodopsin-G-protein complex links the α5 helix to GDP release.Nature structural & molecular biology · 2014Article
- Molecular basis of cannabinoid CB1 receptor coupling to the G protein heterotrimer Gαiβγ: identification of key CB1 contacts with the C-terminal helix α5 of Gαi.The Journal of biological chemistry · 2013Article
- Linking receptor activation to changes in Sw I and II of Gα proteins.Journal of structural biology · 2013Article
- Conformational flexibility and structural dynamics in GPCR-mediated G protein activation: a perspective.Journal of molecular biology · 2013Review
- Myristoylation exerts direct and allosteric effects on Gα conformation and dynamics in solution.Biochemistry · 2012Article
- Allosteric mechanisms of G protein-Coupled Receptor signaling: a structural perspective.Methods in molecular biology (Clifton, N.J.) · 2012Article
- Interaction of a G protein with an activated receptor opens the interdomain interface in the alpha subunit.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Coupling efficiency of rhodopsin and transducin in bicelles.Biochemistry · 2011Article
- Trp fluorescence reveals an activation-dependent cation-pi interaction in the Switch II region of Galphai proteins.Protein science : a publication of the Protein Society · 2009Article
- Structural and kinetic modeling of an activating helix switch in the rhodopsin-transducin interface.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Heterotrimeric G proteins (Galphabetagamma) transmit signals from activated G protein-coupled receptors (GPCRs) to downstream effectors through a guanine nucleotide signaling cycle. Numerous studies indicate that the carboxy-terminal alpha5 helix of Galpha subunits participates in Galpha-receptor binding, and previous EPR studies suggest this receptor-mediated interaction induces a rotation and translation of the alpha5 helix of the Galpha subunit [Oldham, W. M., et al. (2006) Nat. Struct. Mol. Biol. 13, 772-777]. On the basis of this result, an engineered disulfide bond was designed to constrain the alpha5 helix of Galpha(i1) into its EPR-measured receptor-associated conformation through the introduction of cysteines at position 56 in the alpha1 helix and position 333 in the alpha5 helix (I56C/Q333C Galpha(i1)). A functional mimetic of the EPR-measured alpha5 helix dipole movement upon receptor association was additionally created by introduction of a positive charge at the amino terminus of this helix, D328R Galpha(i1). Both proteins exhibit a dramatically elevated level of basal nucleotide exchange. The 2.9 A resolution crystal structure of I56C/Q333C Galpha(i1) in complex with GDP-AlF(4)(-) reveals the shift of the alpha5 helix toward the guanine nucleotide binding site that is anticipated by EPR measurements. The structure of the I56C/Q333C Galpha(i1) subunit further revealed altered positions for the switch regions and throughout the Galpha(i1) subunit, accompanied by significantly elevated crystallographic temperature factors. Combined with previous evidence in the literature, the structural analysis supports the critical role of electrostatics of the alpha5 helix dipole and overall conformational variability during nucleotide release.
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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.