ArticleProtein engineering, design & selection : PEDS2015
Structural and dynamic properties that govern the stability of an engineered fibronectin type III domain.
Article in Protein engineering, design & selection : PEDS, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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
22 citing papers in PubMed, 42 citations in OpenAlex.
- Multi-dimensional orchestration of binders for improved CAR-T immunotherapy.Cancer letters · 2026Review
- Design of Cell-Penetrating Domain Antibodies via a Genetically Encoded β-Lactam Amino Acid.Angewandte Chemie (International ed. in English) · 2025Article
- Proteomic Evidence for Amyloidogenic Cross-Seeding in Fibrinaloid Microclots.International journal of molecular sciences · 2024Article
- mRNA Display Pipeline for Protein Biosensor Construction.ACS sensors · 2024Article
- Article
- Potential of polylactic-co-glycolic acid (PLGA) for delivery Jembrana disease DNA vaccine Model (pEGFP-C1-tat).Journal of veterinary science · 2021Article
- Protein haploinsufficiency drivers identify MYBPC3 variants that cause hypertrophic cardiomyopathy.The Journal of biological chemistry · 2021Article
- Molecular Inversion Probe-Based Sequencing ofInternational journal of molecular sciences · 2021Article
- Improved thermostability of creatinase from Alcaligenes Faecalis through non-biased phylogenetic consensus-guided mutagenesis.Microbial cell factories · 2020Article
- Loss of TNR causes a nonprogressive neurodevelopmental disorder with spasticity and transient opisthotonus.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Article
- Review
- The use of consensus sequence information to engineer stability and activity in proteins.Methods in enzymology · 2020Article
- Engineering selective competitors for the discrimination of highly conserved protein-protein interaction modules.Nature communications · 2019Article
- De Novo Isolation & Affinity Maturation of yeast-displayed Virion-binding human fibronectin domains by flow cytometric screening against Virions.Journal of biological engineering · 2019Article
- Electrostatic Interactions in Protein Structure, Folding, Binding, and Condensation.Chemical reviews · 2018Review
- BOC is a modifier gene in holoprosencephaly.Human mutation · 2017Article
- Creating a Homeodomain with High Stability and DNA Binding Affinity by Sequence Averaging.Journal of the American Chemical Society · 2017Article
- Circumventing the stability-function trade-off in an engineered FN3 domain.Protein engineering, design & selection : PEDS · 2016Article
- Smoothing a rugged protein folding landscape by sequence-based redesign.Scientific reports · 2016Article
- Electrostatic effects on the folding stability of FKBP12.Protein engineering, design & selection : PEDS · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Consensus protein design is a rapid and reliable technique for the improvement of protein stability, which relies on the use of homologous protein sequences. To enhance the stability of a fibronectin type III (FN3) domain, consensus design was employed using an alignment of 2123 sequences. The resulting FN3 domain, FN3con, has unprecedented stability, with a melting temperature >100°C, a ΔG(D-N) of 15.5 kcal mol(-1) and a greatly reduced unfolding rate compared with wild-type. To determine the underlying molecular basis for stability, an X-ray crystal structure of FN3con was determined to 2.0 Å and compared with other FN3 domains of varying stabilities. The structure of FN3con reveals significantly increased salt bridge interactions that are cooperatively networked, and a highly optimized hydrophobic core. Molecular dynamics simulations of FN3con and comparison structures show the cooperative power of electrostatic and hydrophobic networks in improving FN3con stability. Taken together, our data reveal that FN3con stability does not result from a single mechanism, but rather the combination of several features and the removal of non-conserved, unfavorable interactions. The large number of sequences employed in this study has most likely enhanced the robustness of the consensus design, which is now possible due to the increased sequence availability in the post-genomic era. These studies increase our knowledge of the molecular mechanisms that govern stability and demonstrate the rising potential for enhancing stability via the consensus method.
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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.