ArticleProceedings of the National Academy of Sciences of the United States of America2018
GEF mechanism revealed by the structure of SmgGDS-558 and farnesylated RhoA complex and its implication for a chaperone mechanism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- A Rho GTPase-related gene signature predicts prognosis and reveals an immunosuppressive microenvironment in lung adenocarcinoma: an integrated analysis of bulk and single-cell RNA sequencing data.Scientific reports · 2026Article
- Mapping variant effects on anti-tumor hallmarks of primary human T cells with base-editing screens.Nature biotechnology · 2025Article
- Structural Dynamics of Rho GTPases.Journal of molecular biology · 2025Review
- Small GTP-binding protein GDP dissociation stimulator influences cisplatin-induced acute kidney injury via PERK-dependent ER stress.Communications biology · 2024Article
- Polyisoprenylated cysteinyl amide inhibitors deplete singly polyisoprenylated monomeric G-proteins in lung and breast cancer cell lines.Oncotarget · 2023Article
- Identification of a small RhoA GTPase inhibitor effective in fission yeast and human cells.Open biology · 2023Article
- Regulation of Cdc42 protein turnover modulates the filamentous growth MAPK pathway.The Journal of cell biology · 2022Article
- Structural and biophysical properties of farnesylated KRas interacting with the chaperone SmgGDS-558.Biophysical journal · 2022Article
- Loss of KAP3 decreases intercellular adhesion and impairs intracellular transport of laminin in signet ring cell carcinoma of the stomach.Scientific reports · 2022Article
- Review
- Review
- SmgGDS: An Emerging Master Regulator of Prenylation and Trafficking by Small GTPases in the Ras and Rho Families.Frontiers in molecular biosciences · 2021Review
- Combined Proteomic and Genetic Interaction Mapping Reveals New RAS Effector Pathways and Susceptibilities.Cancer discovery · 2020Article
- Chromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma.Nature cell biology · 2020Article
- Functions for Cdc42p BEM adaptors in regulating a differentiation-type MAP kinase pathway.Molecular biology of the cell · 2020Article
- Splice switching an oncogenic ratio of SmgGDS isoforms as a strategy to diminish malignancy.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Structural Insights into the Regulation Mechanism of Small GTPases by GEFs.Molecules (Basel, Switzerland) · 2019Review
- Structural underpinnings of Ric8A function as a G-protein α-subunit chaperone and guanine-nucleotide exchange factor.Nature communications · 2019Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SmgGDS has dual functions in cells and regulates small GTPases as both a guanine nucleotide exchange factor (GEF) for the Rho family and a molecular chaperone for small GTPases possessing a C-terminal polybasic region followed by four C-terminal residues called the CaaX motif, which is posttranslationally prenylated at its cysteine residue. Our recent structural work revealed that SmgGDS folds into tandem copies of armadillo-repeat motifs (ARMs) that are not present in other GEFs. However, the precise mechanism of GEF activity and recognition mechanism for the prenylated CaaX motif remain unknown because SmgGDS does not have a typical GEF catalytic domain and lacks a pocket to accommodate a prenyl group. Here, we aimed to determine the crystal structure of the SmgGDS/farnesylated RhoA complex. We found that SmgGDS induces a significant conformational change in the switch I and II regions that opens up the nucleotide-binding site, with the prenyl group fitting into the cryptic pocket in the N-terminal ARMs. Taken together, our findings could advance the understanding of the role of SmgGDS and enable drug design strategies for targeting SmgGDS and small GTPases.
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