SwitCCh: Metal‐Site Design for Controlling the Assembly of a Coiled‐Coil Homodimer
Open accessAbstract
Conformational change of proteins in response to chemical or physical signals is the underlying principle of many regulatory and transport mechanisms in biological systems. The ability to design proteins the conformational state of which can be precisely and reversibly controlled would facilitate the development of molecular machines tailored for specific applications. Here we explore metal‐binding site design to engineer a peptide‐based conformational switch called SwitCCh that assembles into a homodimeric coiled‐coil in response to the addition of Zn II ions or low pH. Addition of Zn II promoted formation of a parallel homodimer with an increase in thermal stability by more than 30 °C. The peptide could be reversibly cycled between the coiled‐coil and random conformation. Furthermore, the SwitCCh peptide was orthogonal to the previously developed coiled‐coil dimer set, indicating it could be used for regulated self‐assembly of coiled‐coil based nanostructures and materials.
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Achieving the desired balance between multiple target coiled-coil states often requires several rounds of trial-and-error and a detailed understanding of the energetic factors that discriminate between alternative topologies and oligomerization states.
“While this has been accomplished in a number of cases,18−31 achieving the desired balance between multiple target coiled-coil states often requires several rounds of trial-and-error and a detailed understanding of the energetic factors that discriminate between alternative topologies and oligomerization states.”
From Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints (2025) · cites this paper as [26]
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- Authors
- Aupič, J., Lapenta, F., & Jerala, R.
- Affiliations
- University of Ljubljana (SI)
- EN-FIST Centre of Excellence (Slovenia) (SI)
- Corresponding author
- Jerala, Roman
- Venue
- ChemBioChem
- Publisher
- Wiley
- Published
- 2018-10-30
- Volume
- 19
- Issue
- 23
- Pages
- 2453-2457
- ISSN
- 1439-4227 (ISSN-L)
- 1439-7633
- OpenAlex
- W2892868407
- Cited by
- 24
- References
- 0
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 5
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- Locations
- ChemBioChem (publishedVersion)
- PubMed (publishedVersion)
- DiRROS repository (University of Maribor) (acceptedVersion)
- Funders
- Seventh Framework Programme (ERASYNBIO1-006, MediSURF (project3193))
- European Cooperation in Science and Technology (CM-1306, CM-1304)
- H2020 Marie Skłodowska-Curie Actions (MSC-RTN 642157)
- International Centre for Genetic Engineering and Biotechnology (CRP/SLO14-03)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
- Physical Sciences › Chemistry › Organic Chemistry › Supramolecular Chemistry and Complexes
- Keywords
- zinc binding, conformational switching, peptide self-assembly, pH-responsive assembly, thermal stability, protein design, molecular machines, nanostructures
- MeSH terms
- Protein Conformation, alpha-Helical, Amino Acid Sequence, Binding Sites, Copper, Hydrogen-Ion Concentration, Mutation, Protein Binding, Proteins, Zinc, Protein Multimerization, Molecular Dynamics Simulation, Molecular Docking Simulation
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