ArticleJournal of molecular biology2009
Effect of interdomain linker length on an antagonistic folding-unfolding equilibrium between two protein domains.
Article in Journal of molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- 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
- Enhancing response of a protein conformational switch by using two disordered ligand binding domains.Frontiers in molecular biosciences · 2023Article
- Engineering protein and DNA tools for creating DNA-dependent protein switches.Methods in enzymology · 2022Article
- Structure-based design of a photoswitchable affibody scaffold.Protein science : a publication of the Protein Society · 2021Article
- A Single Protein Disruption Site Results in Efficient Reassembly by Multiple Engineering Methods.Biophysical journal · 2019Article
- Converting a Periplasmic Binding Protein into a Synthetic Biosensing Switch through Domain Insertion.BioMed research international · 2019Review
- Enhancement of binding avidity by bivalent binding enables PrPSc-specific detection by anti-PrP monoclonal antibody 132.PloS one · 2019Article
- A pH Switch for β-Sheet Protein Folding.Angewandte Chemie (International ed. in English) · 2017Article
- Influence of Secondary-Structure Folding on the Mutually Exclusive Folding Process of GL5/I27 Protein: Evidence from Molecular Dynamics Simulations.International journal of molecular sciences · 2016Article
- An Internal Disulfide Locks a Misfolded Aggregation-prone Intermediate in Cataract-linked Mutants of Human γD-Crystallin.The Journal of biological chemistry · 2016Article
- Precise assembly of complex beta sheet topologies from de novo designed building blocks.eLife · 2015Article
- Engineered Domain Swapping as an On/Off Switch for Protein Function.Chemistry & biology · 2015Article
- Cytosolic selection systems to study protein stability.Journal of bacteriology · 2014Article
- Chemical biology strategies for posttranslational control of protein function.Chemistry & biology · 2014Review
- Optical control of protein-protein interactions via blue light-induced domain swapping.Biochemistry · 2014Article
- Insertion of endocellulase catalytic domains into thermostable consensus ankyrin scaffolds: effects on stability and cellulolytic activity.Applied and environmental microbiology · 2013Article
- A circularly permuted photoactive yellow protein as a scaffold for photoswitch design.Biochemistry · 2013Article
- The thermodynamic basis for viral RNA detection by the RIG-I innate immune sensor.The Journal of biological chemistry · 2012Article
- Designing redox potential-controlled protein switches based on mutually exclusive proteins.Protein science : a publication of the Protein Society · 2012Article
- Protein conformational switches: from nature to design.Chemistry (Weinheim an der Bergstrasse, Germany) · 2012Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Fusion of one protein domain with another is a common event in both evolution and protein engineering experiments. When insertion is at an internal site (e.g., a surface loop or turn), as opposed to one of the termini, conformational strain can be introduced into both domains. Strain is manifested by an antagonistic folding-unfolding equilibrium between the two domains, which we previously showed can be parameterized by a coupling free-energy term (DeltaG(X)). The extent of strain is predicted to depend primarily on the ratio of the N-to-C distance of the guest protein to the distance between ends of the surface loop in the host protein. Here, we test that hypothesis by inserting ubiquitin (Ub) into the bacterial ribonuclease barnase (Bn), using peptide linkers from zero to 10 amino acids each. DeltaG(X) values are determined by measuring the extent to which Co(2+) binding to an engineered site on the Ub domain destabilizes the Bn domain. All-atom, unforced Langevin dynamics simulations are employed to gain structural insight into the mechanism of mechanically induced unfolding. Experimental and computational results find that the two domains are structurally and energetically uncoupled when linkers are long and that DeltaG(X) increases with decreasing linker length. When the linkers are fewer than two amino acids, strain is so great that one domain unfolds the other. However, the protein is able to refold as dimers and higher-order oligomers. The likely mechanism is a three-dimensional domain swap of the Bn domain, which relieves conformational strain. The simulations suggest that an effective route to mechanical unfolding begins with disruption of the hydrophobic core of Bn near the Ub insertion site.
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