ArticlePLoS pathogens2012
A P-loop mutation in Gα subunits prevents transition to the active state: implications for G-protein signaling in fungal pathogenesis.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Article
- G Protein Activation Occurs via a Largely Universal Mechanism.The journal of physical chemistry. B · 2024Article
- The mechanism ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Hydrophobic cue-induced appressorium formation depends on MoSep1-mediated MoRgs7 phosphorylation and internalization in Magnaporthe oryzae.PLoS genetics · 2023Article
- Phenotypic Diversity in GNAO1 Patients: A Comprehensive Overview of Variants and Phenotypes.Human mutation · 2023Review
- Novel de novo pathogenic variant in the GNAI1 gene as a cause of severe disorders of intellectual development.Journal of human genetics · 2022Article
- Genetic modeling of GNAO1 disorder delineates mechanisms of Gαo dysfunction.Human molecular genetics · 2022Article
- GNAQ mutations drive port wine birthmark-associated Sturge-Weber syndrome: A review of pathobiology, therapies, and current models.Frontiers in human neuroscience · 2022Review
- Gαo is a major determinant of cAMP signaling in the pathophysiology of movement disorders.Cell reports · 2021Article
- An atypical heterotrimeric Gα protein has substantially reduced nucleotide binding but retains nucleotide-independent interactions with its cognate RGS protein and Gβγ dimer.Journal of biomolecular structure & dynamics · 2020Article
- Article
- Structural design principles that underlie the multi-specific interactions of GαScientific reports · 2019Article
- Article
- Directly light-regulated binding of RGS-LOV photoreceptors to anionic membrane phospholipids.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Movement disorder inNeurology · 2017Article
- Cpk2, a Catalytic Subunit of Cyclic AMP-PKA, Regulates Growth and Pathogenesis in Rice Blast.Frontiers in microbiology · 2017Article
- A G-protein Subunit-α11 Loss-of-Function Mutation, Thr54Met, Causes Familial Hypocalciuric Hypercalcemia Type 2 (FHH2).Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Article
- Integration of G protein α (Gα) signaling by the regulator of G protein signaling 14 (RGS14).The Journal of biological chemistry · 2015Article
- The late endosomal HOPS complex anchors active G-protein signaling essential for pathogenesis in magnaporthe oryzae.PLoS pathogens · 2013Article
- Crystal structures of the scaffolding protein LGN reveal the general mechanism by which GoLoco binding motifs inhibit the release of GDP from Gαi.The Journal of biological chemistry · 2012Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Heterotrimeric G-proteins are molecular switches integral to a panoply of different physiological responses that many organisms make to environmental cues. The switch from inactive to active Gαβγ heterotrimer relies on nucleotide cycling by the Gα subunit: exchange of GTP for GDP activates Gα, whereas its intrinsic enzymatic activity catalyzes GTP hydrolysis to GDP and inorganic phosphate, thereby reverting Gα to its inactive state. In several genetic studies of filamentous fungi, such as the rice blast fungus Magnaporthe oryzae, a G42R mutation in the phosphate-binding loop of Gα subunits is assumed to be GTPase-deficient and thus constitutively active. Here, we demonstrate that Gα(G42R) mutants are not GTPase deficient, but rather incapable of achieving the activated conformation. Two crystal structure models suggest that Arg-42 prevents a typical switch region conformational change upon Gα(i1)(G42R) binding to GDP·AlF(4)(-) or GTP, but rotameric flexibility at this locus allows for unperturbed GTP hydrolysis. Gα(G42R) mutants do not engage the active state-selective peptide KB-1753 nor RGS domains with high affinity, but instead favor interaction with Gβγ and GoLoco motifs in any nucleotide state. The corresponding Gα(q)(G48R) mutant is not constitutively active in cells and responds poorly to aluminum tetrafluoride activation. Comparative analyses of M. oryzae strains harboring either G42R or GTPase-deficient Q/L mutations in the Gα subunits MagA or MagB illustrate functional differences in environmental cue processing and intracellular signaling outcomes between these two Gα mutants, thus demonstrating the in vivo functional divergence of G42R and activating G-protein mutants.
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