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Molecular basis of coiled-coil formation
Open accessAbstract
Coiled coils have attracted considerable interest as design templates in a wide range of applications. Successful coiled-coil design strategies therefore require a detailed understanding of coiled-coil folding. One common feature shared by coiled coils is the presence of a short autonomous helical folding unit, termed “trigger sequence,” that is indispensable for folding. Detailed knowledge of trigger sequences at the molecular level is thus key to a general understanding of coiled-coil formation. Using a multidisciplinary approach, we identify and characterize here the molecular determinants that specify the helical conformation of the monomeric early folding intermediate of the GCN4 coiled coil. We demonstrate that a network of hydrogen-bonding and electrostatic interactions stabilize the trigger-sequence helix. This network is rearranged in the final dimeric coiled-coil structure, and its destabilization significantly slows down GCN4 leucine zipper folding. Our findings provide a general explanation for the molecular mechanism of coiled-coil formation.
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“While in nature folding and association of coiled coils occur simultaneously,94 they can be studied separately in silico due to free energy being a state function.”
From Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints (2025) · cites this paper as [94]
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Metadata
- Authors
- Steinmetz, M. O., Jelesarov, I., Matousek, W. M., Honnappa, S., Jahnke, W., Missimer, J. H., Frank, S., Alexandrescu, A. T., & Kammerer, R. A.
- Affiliations
- Paul Scherrer Institute (CH)
- University of Zurich (CH)
- University of Connecticut (US)
- *Biomolecular Research, Structural Biology, Paul Scherrer Institut, CH-5232 Villigen PSI, Switzerland;
- Novartis (Switzerland) (CH)
- F. Hoffmann-La Roche AG (CH)
- Wellcome Centre for Cell-Matrix Research (GB)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-04-24
- Volume
- 104
- Issue
- 17
- Pages
- 7062-7067
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1855353
- OpenAlex
- W2032892814
- Cited by
- 136
- References
- 61
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 9 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 7 · 2016: 5 · 2015: 7 · 2014: 10 · 2013: 13 · 2012: 15
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Wellcome Trust
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (109423)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- GCN4, leucine zipper, helix stabilization, hydrogen bonding, electrostatic interactions, protein folding mechanism, dimerization
- MeSH terms
- Arginine, DNA-Binding Proteins, Hydrogen-Ion Concentration, Kinetics, Magnetic Resonance Spectroscopy, Peptides, Solutions, Thermodynamics, Transcription Factors, Leucine Zippers, Protein Folding, Amino Acid Substitution, Saccharomyces cerevisiae Proteins, Mutant Proteins, Basic-Leucine Zipper Transcription Factors
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