Multidomain structure and correlated dynamics determined by self-consistent FRET networks
Open accessAbstract
We present an approach that enables us to simultaneously access structure and dynamics of a multidomain protein in solution. Dynamic domain arrangements are experimentally determined by combining self-consistent networks of distance distributions with known domain structures. Local structural dynamics are correlated with the global arrangements by analyzing networks of time-resolved single-molecule fluorescence parameters. The strength of this hybrid approach is shown by an application to the flexible multidomain protein Hsp90. The average solution structure of Hsp90's closed state resembles the known X-ray crystal structure with Angstrom precision. The open state is represented by an ensemble of conformations with interdomain fluctuations of up to 25 Å. The data reveal a state-specific suppression of the submillisecond fluctuations by dynamic protein-protein interaction. Finally, the method enables localization and functional characterization of dynamic elements and domain interfaces.
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Biophysical data indicate that apo-Hsp90 populates a dynamic ensemble of extended conformations in solution.
“Biophysical data indicate that apo-Hsp90 populates a dynamic ensemble of extended conformations in solution (11, 12).”
From Client binding shifts the populations of dynamic Hsp90 conformations through an allosteric network (2021) · cites this paper as [11]
The Hsp90 dimer still samples a range of open states when bound to ATP.
“In spite of this local domain arrangement, the Hsp90 dimer, overall, still samples a range of open states when bound to ATP, as indicated by SAXS data and consistent with previously reported fluorescence resonance energy transfer experiments (11).”
From Client binding shifts the populations of dynamic Hsp90 conformations through an allosteric network (2021) · cites this paper as [11]
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- Authors
- Hellenkamp, B., Wortmann, P., Kandzia, F., Zacharias, M., & Hugel, T.
- Affiliations
- University of Freiburg (DE)
- Technical University of Munich (DE)
- Corresponding author
- Hugel, Thorsten
- Venue
- Nature Methods
- Published
- 2016-12-05
- Volume
- 14
- Issue
- 2
- Pages
- 174-180
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- PMC
- PMC5289555
- OpenAlex
- W2560512058
- Cited by
- 137
- References
- 35
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 14 · 2023: 9 · 2022: 8 · 2021: 17 · 2020: 17 · 2019: 22 · 2018: 21 · 2017: 17
- FWCI
- 10.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Methods (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- HSP90, multidomain proteins, single-molecule FRET, protein dynamics in solution, protein-protein interaction, protein conformational ensembles, domain interfaces
- MeSH terms
- Protein Domains, Models, Molecular, Crystallography, X-Ray, HSP90 Heat-Shock Proteins, Fluorescence Resonance Energy Transfer, Molecular Dynamics Simulation
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