ArticleTraffic (Copenhagen, Denmark)2020
Preprotein signature for full susceptibility to the co-translational translocation inhibitor cyclotriazadisulfonamide.
Article in Traffic (Copenhagen, Denmark), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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
12 citing papers in PubMed.
- Are Signal Peptides Hidden Regulators of Neurodegenerative Disease?Biomedicines · 2026Review
- Targeted downmodulation of OXTR and Cx43 in the myometrium by SERTIs as a novel tocolytic strategy.Uterine research · 2026Article
- Signal Peptides: From Molecular Mechanisms to Applications in Protein and Vaccine Engineering.Biomolecules · 2025Review
- Inhibition of TSH Receptor Expression by a Cyclotriazadisulfonamide as a Potential Treatment of Graves Hyperthyroidism.Endocrinology · 2025Article
- Rough microsomes isolated from snap-frozen canine pancreatic tissue retain their co-translational translocation functionality.Biology methods & protocols · 2025Article
- A common mechanism of Sec61 translocon inhibition by small molecules.Nature chemical biology · 2023Article
- Structural insights into TRAP association with ribosome-Sec61 complex and translocon inhibition by a CADA derivative.Science advances · 2023Article
- Effects of a Shift of the Signal Peptide Cleavage Site in Signal Peptide Variant on the Synthesis and Secretion of SARS-CoV-2 Spike Protein.Molecules (Basel, Switzerland) · 2022Article
- Reduced DNAJC3 Expression Affects Protein Translocation across the ER Membrane and Attenuates the Down-Modulating Effect of the Translocation Inhibitor Cyclotriazadisulfonamide.International journal of molecular sciences · 2022Article
- Inhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway.International journal of molecular sciences · 2021Review
- Small Molecule Cyclotriazadisulfonamide Abrogates the Upregulation of the Human Receptors CD4 and 4-1BB and Suppresses In Vitro Activation and Proliferation of T Lymphocytes.Frontiers in immunology · 2021Article
- The signal peptide as a new target for drug design.Bioorganic & medicinal chemistry letters · 2020Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Cyclotriazadisulfonamide (CADA) inhibits the co-translational translocation of human CD4 (huCD4) into the endoplasmic reticulum lumen in a signal peptide (SP)-dependent way. We propose that CADA binds the nascent huCD4 SP in a folded conformation within the translocon resembling a normally transitory state during translocation. Here, we used alanine scanning on the huCD4 SP to identify the signature for full susceptibility to CADA. In accordance with our previous work, we demonstrate that residues in the vicinity of the hydrophobic h-region are critical for sensitivity to CADA. In particular, exchanging Gln-15, Val-17 or Pro-20 in the huCD4 SP for Ala resulted in a resistant phenotype. Together with positively charged residues at the N-terminal portion of the mature protein, these residues mediate full susceptibility to the co-translational translocation inhibitory activity of CADA towards huCD4. In addition, sensitivity to CADA is inversely related to hydrophobicity in the huCD4 SP. In vitro translocation experiments confirmed that the general hydrophobicity of the h-domain and positive charges in the mature protein are key elements that affect both the translocation efficiency of huCD4 and the sensitivity towards CADA. Besides these two general SP parameters that determine the functionality of the signal sequence, unique amino acid pairs (L14/Q15 and L19/P20) in the SP hydrophobic core add specificity to the sensitivity signature for a co-translational translocation inhibitor.
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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 OpenQuestion graph.