ArticleJournal of the American Chemical Society2014
Expanding Anfinsen's principle: contributions of synonymous codon selection to rational protein design.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Synonymous but Not Silent: The Codon Usage Code for Gene Expression and Protein Folding.Annual review of biochemistry · 2021Pooled it
- The Tor pathway, ribosome concentration, and wobble decoding mediate inhibitory effects of the Leu-Pro CUC-CCG codon pair inRNA (New York, N.Y.) · 2026Article
- Genome-wide association study and KASP development for growth and leaf traits in Populus deltoides.BMC genomics · 2026Article
- Early-stage Determinants of T1-S1 Conformations in Kv1.3 Channels.Journal of molecular biology · 2025Article
- Native CFTR codon bias controls translation rate to balance off-pathway aggregation and channel function by conformational imprinting.Scientific reports · 2025Article
- Nuclear effects play an important role in determining codon usage-dependent human gene expression.Nature communications · 2025Article
- Disease-associated Kv1.3 Variants are Energy Compromised with Impaired Nascent Chain Folding.Journal of molecular biology · 2025Article
- Codon usage modulates the relationship between the burden and yield of protein overexpression.Journal of biological engineering · 2025Article
- Seesaw protein: Design of a protein that adopts interconvertible alternative functional conformations and its dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Current landscape of mRNA technologies and delivery systems for new modality therapeutics.Journal of biomedical science · 2024Review
- Synonymous codon substitutions modulate transcription and translation of a divergent upstream gene by modulating antisense RNA production.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Translation Rates and Protein Folding.Journal of molecular biology · 2024Review
- The Effects of Codon Usage on Protein Structure and Folding.Annual review of biophysics · 2024Review
- Ser/Leu-swapped cell-free translation system constructed with natural/in vitro transcribed-hybrid tRNA set.Nature communications · 2024Article
- Molecular bases for strong phenotypic effects of single synonymous codon substitutions in the E. coli ccdB toxin gene.BMC genomics · 2023Article
- An exploratory in silico comparison of open-source codon harmonization tools.Microbial cell factories · 2023Article
- mRNA-based vaccines and therapeutics: an in-depth survey of current and upcoming clinical applications.Journal of biomedical science · 2023Review
- Fluid protein fold space and its implications.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- A BioBricks Metabolic Engineering Platform for the Biosynthesis of Anthracyclinones inACS synthetic biology · 2022Article
- The High Mutational Sensitivity of ccdA Antitoxin Is Linked to Codon Optimality.Molecular biology and evolution · 2022Article
25 more citing papers are in PubMed but not listed here.
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Abstract
Anfinsen's principle asserts that all information required to specify the structure of a protein is encoded in its amino acid sequence. However, during protein synthesis by the ribosome, the N-terminus of the nascent chain can begin to fold before the C-terminus is available. We tested whether this cotranslational folding can alter the folded structure of an encoded protein in vivo, versus the structure formed when refolded in vitro. We designed a fluorescent protein consisting of three half-domains, where the N- and C-terminal half-domains compete with each other to interact with the central half-domain. The outcome of this competition determines the fluorescence properties of the resulting folded structure. Upon refolding after chemical denaturation, this protein produced equimolar amounts of the N- and C-terminal folded structures, respectively. In contrast, translation in Escherichia coli resulted in a 2-fold enhancement in the formation of the N-terminal folded structure. Rare synonymous codon substitutions at the 5' end of the C-terminal half-domain further increased selection for the N-terminal folded structure. These results demonstrate that the rate at which a nascent protein emerges from the ribosome can specify the folded structure of a protein.
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