ArticleJournal of the American Chemical Society2018
An Atypical Mechanism of Split Intein Molecular Recognition and Folding.
Article in Journal of the American Chemical Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Split Intein-Mediated Engineering of Bacteriocins Through Backbone Circularization, Modular Assembly of Chimeras, and Inducible Circularization.Biomolecules · 2026Article
- Generating Ultra-Fast Protein trans-Splicing of a Cysteine-Less and Semisynthetic Split Intein for Chemical Protein Labeling.Chembiochem : a European journal of chemical biology · 2026Article
- Engineering Targeted Gene Delivery Systems for Primary Hereditary Skeletal Myopathies: Current Strategies and Future Perspectives.Biomedicines · 2025Review
- A Unique THN Motif Is Critical for Enabling Efficient C-Terminal Traceless Cleavage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Intracellular protein editing enables incorporation of noncanonical residues in endogenous proteins.Science (New York, N.Y.) · 2025Article
- Protein editing using a coordinated transposition reaction.Science (New York, N.Y.) · 2025Article
- A cysteine-less and ultra-fast split intein rationally engineered from being aggregation-prone to highly efficient in protein trans-splicing.Nature communications · 2025Article
- Conditional Split Inteins: Adaptable Tools for Programming Protein Functions.International journal of molecular sciences · 2025Review
- Systemic delivery of full-length dystrophin in Duchenne muscular dystrophy mice.Nature communications · 2024Article
- Extein residues regulate the catalytic function of Spl DnaX intein enzyme by restricting the near-attack conformations of the active-site residues.Protein science : a publication of the Protein Society · 2023Article
- Nature-inspired protein ligation and its applications.Nature reviews. Chemistry · 2023Review
- A Conserved Histidine Residue Drives Extein Dependence in an Enhanced Atypically Split Intein.Journal of the American Chemical Society · 2022Article
- Live-cell protein engineering with an ultra-short split intein.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- In situ chromatin interactomics using a chemical bait and trap approach.Nature chemistry · 2020Article
- Chemoenzymatic Semisynthesis of Proteins.Chemical reviews · 2020Review
- A mesophilic cysteine-less split intein for proteinProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Proximity Induced Splicing Utilizing Caged Split Inteins.Journal of the American Chemical Society · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Split inteins associate to trigger protein splicing in trans, a post-translational modification in which protein sequences fused to the intein pair are ligated together in a traceless manner. Recently, a family of naturally split inteins has been identified that is split at a noncanonical location in the primary sequence. These atypically split inteins show considerable promise in protein engineering applications; however, the mechanism by which they associate is unclear and must be different from that of previously characterized canonically split inteins due to unique topological restrictions. Here, we use a consensus design strategy to generate an atypical split intein pair (Cat) that has greatly improved activity and is amenable to detailed biochemical and biophysical analysis. Guided by the solution structure of Cat, we show that the association of the fragments involves a disorder-to-order structural transition driven by hydrophobic interactions. This molecular recognition mechanism satisfies the topological constraints of the intein fold and, importantly, ensures that premature chemistry does not occur prior to fragment complementation. Our data lead a common blueprint for split intein complementation in which localized structural rearrangements are used to drive folding and regulate protein-splicing activity.
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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.