ArticleBiochemistry2017
Substrate Recognition of MARTX Ras/Rap1-Specific Endopeptidase.
Article in Biochemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Engineered subtilisin protease degrades active KRAS in cancer cells leading to differential cell targeting.Research square · 2026Article
- Engineered subtilisin protease degrades active KRAS in cancer cells, leading to differential cell targeting.bioRxiv : the preprint server for biology · 2026Article
- Substrate specificity in a designed RAS-targeting protease is coupled to active site and distal motions.bioRxiv : the preprint server for biology · 2026Article
- Expression of a RAS degrader via synthetic nanocarrier-mediated mRNA delivery reduces pancreatic tumors.bioRxiv : the preprint server for biology · 2025Article
- RAS degraders: The new frontier for RAS-driven cancers.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Proteolytic pan-RAS Cleavage Leads to Tumor Regression in Patient-derived Pancreatic Cancer Xenografts.Molecular cancer therapeutics · 2022Article
- RAS specific protease induces irreversible growth arrest via p27 in several KRAS mutant colorectal cancer cell lines.Scientific reports · 2021Article
- A Computational Investigation of In Vivo Cytosolic Protein Delivery for Cancer Therapy.Pharmaceutics · 2021Article
- Anthrax Protective Antigen Retargeted with Single-Chain Variable Fragments Delivers Enzymes to Pancreatic Cancer Cells.Chembiochem : a European journal of chemical biology · 2020Article
- Delivering a RAS protease halts tumor growth.Oncotarget · 2020Article
- An engineered chimeric toxin that cleaves activated mutant and wild-type RAS inhibits tumor growth.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- RRSP and RID Effector Domains Dominate the Virulence Impact of Vibrio vulnificus MARTX Toxin.The Journal of infectious diseases · 2019Article
- The Modes of Action of MARTX Toxin Effector Domains.Toxins · 2018Review
- Ancestral gene acquisition as the key to virulence potential in environmental Vibrio populations.The ISME journal · 2018Article
- Structural basis of inactivation of Ras and Rap1 small GTPases by Ras/Rap1-specific endopeptidase from the sepsis-causing pathogenThe Journal of biological chemistry · 2018Article
- The bacterial Ras/Rap1 site-specific endopeptidase RRSP cleaves Ras through an atypical mechanism to disrupt Ras-ERK signaling.Science signaling · 2018Article
- Desmoplakin maintains gap junctions by inhibiting Ras/MAPK and lysosomal degradation of connexin-43.The Journal of cell biology · 2018Article
- Coordinated delivery and function of bacterial MARTX toxin effectors.Molecular microbiology · 2018Review
- The insect pathogenic bacterium Xenorhabdus innexi has attenuated virulence in multiple insect model hosts yet encodes a potent mosquitocidal toxin.BMC genomics · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Ras/Rap1-specific endopeptidase (RRSP) is a cytotoxic effector domain of the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin of highly virulent strains of Vibrio vulnificus. RRSP blocks RAS-MAPK kinase signaling by cleaving Ras and Rap1 within the switch I region between Y32 and D33. Although the RRSP processing site is highly conserved among small GTPases, only Ras and Rap1 have been identified as proteolytic substrates. Here we report that residues Y32 and D33 at the scissile bond play an important role in RRSP substrate recognition, while the nucleotide state of Ras has an only minimal effect. In addition, substrate specificity is generated by residues across the entire switch I region. Indeed, swapping the Ras switch I region into either RalA or RhoA, GTPases that are not recognized by RRSP, generated chimeras that are substrates of RRSP. However, a difference in the processing efficiency of Ras switch I in the context of Ras, RalA, or RhoA indicates that protein regions outside Ras switch I also contribute to efficient RRSP substrate recognition. Moreover, we show that synthetic peptides corresponding to the Ras and Rap1, but not RalA, switch I regions are cleaved by RRSP, demonstrating sequence-specific substrate recognition. In conclusion, this work demonstrates that the GTPase recognition of RRSP is independent of the nucleotide state and is mainly driven by the Ras and Rap1 switch I loop and also influenced by additional protein-protein interactions, increasing the substrate specificity of RRSP.
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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.