ArticleInternational journal of molecular sciences2021
Electrostatic Forces Mediate the Specificity of RHO GTPase-GDI Interactions.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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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.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- Lipid nanoparticles as active biointerfaces: From membrane interaction to systemic dysregulation.Acta pharmaceutica Sinica. B · 2026Review
- Hearing loss associated with CDC42 in mice and humans (Takenouchi-Kosaki syndrome): CDC42 and RHOQ synergistically function in cochlear hair cells.The Journal of biological chemistry · 2026Article
- RHOA at the intersection of inflammation-driven and sporadic colorectal cancer.Frontiers in immunology · 2026Review
- New insights into the classification of the RAC1 P29S hotspot mutation in melanoma as an oncogene.Cancer gene therapy · 2025Article
- Rho-GTPases subfamily: cellular defectors orchestrating viral infection.Cellular & molecular biology letters · 2025Review
- To stay in shape and keep moving: MLL emerges as a new transcriptional regulator of Rho GTPases.Small GTPases · 2023Article
- Spatiotemporal regulation of Rho GTPase signaling during endothelial barrier remodeling.Current opinion in physiology · 2023Review
- Molecular dynamics simulations reveal the inhibition mechanism of Cdc42 by RhoGDI1.Journal of computer-aided molecular design · 2023Article
- The Dual Function of RhoGDI2 in Immunity and Cancer.International journal of molecular sciences · 2023Review
- Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
Abstract
Three decades of research have documented the spatiotemporal dynamics of RHO family GTPase membrane extraction regulated by guanine nucleotide dissociation inhibitors (GDIs), but the interplay of the kinetic mechanism and structural specificity of these interactions is as yet unresolved. To address this, we reconstituted the GDI-controlled spatial segregation of geranylgeranylated RHO protein RAC1 in vitro. Various biochemical and biophysical measurements provided unprecedented mechanistic details for GDI function with respect to RHO protein dynamics. We determined that membrane extraction of RHO GTPases by GDI occurs via a 3-step mechanism: (1) GDI non-specifically associates with the switch regions of the RHO GTPases; (2) an electrostatic switch determines the interaction specificity between the C-terminal polybasic region of RHO GTPases and two distinct negatively-charged clusters of GDI1; (3) a non-specific displacement of geranylgeranyl moiety from the membrane sequesters it into a hydrophobic cleft, effectively shielding it from the aqueous milieu. This study substantially extends the model for the mechanism of GDI-regulated RHO GTPase extraction from the membrane, and could have implications for clinical studies and drug development.
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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 Socratic graph.