ArticleJournal of the American Chemical Society2013
Extein residues play an intimate role in the rate-limiting step of protein trans-splicing.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 84 citations in OpenAlex.
- Article
- Regulation of N-terminal cleavage and splicing in mini-Ter DnaE-3 intein by E23G and R50Q mutations.Biotechnology letters · 2026Article
- Traceless protein semisynthesis in cells using the promiscuous ultra-fast split intein NrdJ-1.Chemical science · 2026Article
- A Tripartite AAV System with Engineered Lox Sites Enables Efficient Delivery of theHuman gene therapy · 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
- Traceless protein semi-synthesis in cells using the promiscuous ultra-fast split intein NrdJ-1.bioRxiv : the preprint server for biology · 2026Article
- Three-Segment Protein Labeling Using a Highly Efficient and Cysteine-Less Split Intein Identified with Computational Prediction of Aggregation Properties.Angewandte Chemie (International ed. in English) · 2025Article
- RP1 Dual-AAV Gene Therapy Preserves Retinal Structure and Ameliorates Photoreceptor Degeneration in a Murine Model of Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2025Article
- Exploring AAV-Mediated Gene Therapy for Inner Ear Diseases: from Preclinical Success to Clinical Potential.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- A Unique THN Motif Is Critical for Enabling Efficient C-Terminal Traceless Cleavage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Split RNA switch orchestrates pre- and post-translational control to enable cell type-specific gene expression.Nature communications · 2025Article
- Cyclization of Short Peptides Designed from Late Embryogenesis Abundant Protein to Improve Stability and Functionality.Chembiochem : a European journal of chemical biology · 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
- Delivering large genes using adeno-associated virus and the CRE-lox DNA recombination system.Human molecular genetics · 2024Article
- In Silico Structural Prediction for the Generation of Novel Performant Midi-Dystrophins Based on Intein-Mediated Dual AAV Approach.International journal of molecular sciences · 2024Article
- Ligation of multiple protein domains using orthogonal inteins with non-native splice junctions.Protein science : a publication of the Protein Society · 2024Article
- Optimization strategies and advances in the research and development of AAV-based gene therapy to deliver large transgenes.Clinical and translational medicine · 2024Review
- 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
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Split inteins play an important role in modern protein semisynthesis techniques. These naturally occurring protein splicing domains can be used for in vitro and in vivo protein modification, peptide and protein cyclization, segmental isotopic labeling, and the construction of biosensors. The most well-characterized family of split inteins, the cyanobacterial DnaE inteins, show particular promise, as many of these can splice proteins in less than 1 min. Despite this fact, the activity of these inteins is context-dependent: certain peptide sequences surrounding their ligation junction (called local N- and C-exteins) are strongly preferred, while other sequences cause a dramatic reduction in the splicing kinetics and yield. These sequence constraints limit the utility of inteins, and thus, a more detailed understanding of their participation in protein splicing is needed. Here we present a thorough kinetic analysis of the relationship between C-extein composition and split intein activity. The results of these experiments were used to guide structural and molecular dynamics studies, which revealed that the motions of catalytic residues are constrained by the second C-extein residue, likely forcing them into an active conformation that promotes rapid protein splicing. Together, our structural and functional studies also highlight a key region of the intein structure that can be re-engineered to increase intein promiscuity.
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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.