ArticlePloS one2012
Charged and hydrophobic surfaces on the a chain of shiga-like toxin 1 recognize the C-terminal domain of ribosomal stalk proteins.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- A fluorescence anisotropy-based competition assay to identify inhibitors against ricin and Shiga toxin ribosome interactions.Analytical biochemistry · 2024Article
- Fragment Screening to Identify Inhibitors Targeting Ribosome Binding of Shiga Toxin 2.ACS infectious diseases · 2024Article
- Structure-Function Analysis of the A1 Subunit of Shiga Toxin 2 with Peptides That Target the P-Stalk Binding Site and Inhibit Activity.Biochemistry · 2024Article
- Structure-based design and optimization of a new class of small molecule inhibitors targeting the P-stalk binding pocket of ricin.Bioorganic & medicinal chemistry · 2024Article
- The Biological Action and Structural Characterization of Eryngitin 3 and 4, Ribotoxin-like Proteins fromInternational journal of molecular sciences · 2023Article
- Synthesis and Structural Characterization of Ricin Inhibitors Targeting Ribosome Binding Using Fragment-Based Methods and Structure-Based Design.Journal of medicinal chemistry · 2021Article
- Structural basis for the interaction of Shiga toxin 2a with a C-terminal peptide of ribosomal P stalk proteins.The Journal of biological chemistry · 2020Article
- Ribosomal stalk proteins RPLP1 and RPLP2 promote biogenesis of flaviviral and cellular multi-pass transmembrane proteins.Nucleic acids research · 2020Article
- Small Molecule Inhibitors Targeting the Interaction of Ricin Toxin A Subunit with Ribosomes.ACS infectious diseases · 2020Article
- Leucine 232 and hydrophobic residues at the ribosomal P stalk binding site are critical for biological activity of ricin.Bioscience reports · 2019Article
- How Ricin Damages the Ribosome.Toxins · 2019Review
- Peptide Mimics of the Ribosomal P Stalk Inhibit the Activity of Ricin A Chain by Preventing Ribosome Binding.Toxins · 2018Article
- Review
- Human ribosomal P1-P2 heterodimer represents an optimal docking site for ricin A chain with a prominent role for P1 C-terminus.Scientific reports · 2017Article
- Differences in Ribosome Binding and Sarcin/Ricin Loop Depurination by Shiga and Ricin Holotoxins.Toxins · 2017Article
- Review
- Ricin uses arginine 235 as an anchor residue to bind to P-proteins of the ribosomal stalk.Scientific reports · 2017Article
- Conserved Arginines at the P-Protein Stalk Binding Site and the Active Site Are Critical for Ribosome Interactions of Shiga Toxins but Do Not Contribute to Differences in the Affinity of the A1 Subunits for the Ribosome.Infection and immunity · 2016Article
- Toxicity of ricin A chain is reduced in mammalian cells by inhibiting its interaction with the ribosome.Toxicology and applied pharmacology · 2016Article
- Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Shiga-like toxins are ribosome-inactivating proteins (RIP) produced by pathogenic E. coli strains that are responsible for hemorrhagic colitis and hemolytic uremic syndrome. The catalytic A(1) chain of Shiga-like toxin 1 (SLT-1), a representative RIP, first docks onto a conserved peptide SD[D/E]DMGFGLFD located at the C-terminus of all three eukaryotic ribosomal stalk proteins and halts protein synthesis through the depurination of an adenine base in the sarcin-ricin loop of 28S rRNA. Here, we report that the A(1) chain of SLT-1 rapidly binds to and dissociates from the C-terminal peptide with a monomeric dissociation constant of 13 µM. An alanine scan performed on the conserved peptide revealed that the SLT-1 A(1) chain interacts with the anionic tripeptide DDD and the hydrophobic tetrapeptide motif FGLF within its sequence. Based on these 2 peptide motifs, SLT-1 A(1) variants were generated that displayed decreased affinities for the stalk protein C-terminus and also correlated with reduced ribosome-inactivating activities in relation to the wild-type A(1) chain. The toxin-peptide interaction and subsequent toxicity were shown to be mediated by cationic and hydrophobic docking surfaces on the SLT-1 catalytic domain. These docking surfaces are located on the opposite face of the catalytic cleft and suggest that the docking of the A(1) chain to SDDDMGFGLFD may reorient its catalytic domain to face its RNA substrate. More importantly, both the delineated A(1) chain ribosomal docking surfaces and the ribosomal peptide itself represent a target and a scaffold, respectively, for the design of generic inhibitors to block the action of RIPs.
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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.