ArticleThe Journal of biological chemistry2012
Modulation of conotoxin structure and function is achieved through a multienzyme complex in the venom glands of cone snails.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Ancestral Sequence Reconstruction Provides Insights into the Structural Diversification and Neofunctionalization of T-superfamily Conotoxins in Conus.Molecular biology and evolution · 2025Article
- An N-Terminally Elongated Peptide From Conus rolani Defines a New Class of Ribbon α-Conotoxins Targeting Muscle nAChRs.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Redox-Active Conopeptide Li520 Has Evolved to Catalyze Oxidative Folding of Conotoxins.ACS omega · 2024Article
- δ-Conotoxin Structure Prediction and Analysis through Large-Scale Comparative and Deep Learning Modeling Approaches.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- High-Throughput Prediction and Design of Novel Conopeptides for Biomedical Research and Development.Biodesign research · 2022Article
- Mining genomes to illuminate the specialized chemistry of life.Nature reviews. Genetics · 2021Review
- Transcriptomic profiling of the medicinal plant Clitoria ternatea: identification of potential genes in cyclotide biosynthesis.Scientific reports · 2020Article
- Heterogeneous-Backbone Foldamer Mimics of a Computationally Designed, Disulfide-Rich Miniprotein.Chembiochem : a European journal of chemical biology · 2019Article
- Periplasmic Expression of 4/7 α-Conotoxin TxIA Analogs inFrontiers in pharmacology · 2019Article
- Ero1-Mediated Reoxidation of Protein Disulfide Isomerase Accelerates the Folding of Cone Snail Toxins.International journal of molecular sciences · 2018Article
- Oxidative Folding of Conopeptides Modified by Conus Protein Disulfide Isomerase.The protein journal · 2017Article
- Plasticity in the Oxidative Folding Pathway of the High Affinity Nerita Versicolor Carboxypeptidase Inhibitor (NvCI).Scientific reports · 2017Article
- Article
- Comparative venomics of Psyttalia lounsburyi and P. concolor, two olive fruit fly parasitoids: a hypothetical role for a GH1 β-glucosidase.Scientific reports · 2016Article
- Rapid expansion of the protein disulfide isomerase gene family facilitates the folding of venom peptides.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Article
- High conopeptide diversity in Conus tribblei revealed through analysis of venom duct transcriptome using two high-throughput sequencing platforms.Marine biotechnology (New York, N.Y.) · 2015Article
- Structure and function of μ-conotoxins, peptide-based sodium channel blockers with analgesic activity.Future medicinal chemistry · 2014Review
- Association between foldability and aggregation propensity in small disulfide-rich proteins.Antioxidants & redox signaling · 2014Article
- Discovery, synthesis, and structure-activity relationships of conotoxins.Chemical reviews · 2014Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The oxidative folding of large polypeptides has been investigated in detail; however, comparatively little is known about the enzyme-assisted folding of small, disulfide-containing peptide substrates. To investigate the concerted effect of multiple enzymes on the folding of small disulfide-rich peptides, we sequenced and expressed protein-disulfide isomerase (PDI), peptidyl-prolyl cis-trans isomerase, and immunoglobulin-binding protein (BiP) from Conus venom glands. Conus PDI was shown to catalyze the oxidation and reduction of disulfide bonds in two conotoxins, α-GI and α-ImI. Oxidative folding rates were further increased in the presence of Conus PPI with the maximum effect observed in the presence of both enzymes. In contrast, Conus BiP was only observed to assist folding in the presence of microsomes, suggesting that additional co-factors were involved. The identification of a complex between BiP, PDI, and nascent conotoxins further suggests that the folding and assembly of conotoxins is a highly regulated multienzyme-assisted process. Unexpectedly, all three enzymes contributed to the folding of the ribbon isomer of α-ImI. Here, we identify this alternative disulfide-linked species in the venom of Conus imperialis, providing the first evidence for the existence of a "non-native" peptide isomer in the venom of cone snails. Thus, ER-resident enzymes act in concert to accelerate the oxidative folding of conotoxins and modulate their conformation and function by reconfiguring disulfide connectivities. This study has evaluated the role of a number of ER-resident enzymes in the folding of conotoxins, providing novel insights into the enzyme-guided assembly of these small, disulfide-rich peptides.
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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.