The Onset of Molecule-Spanning Dynamics in Heat Shock Protein Hsp90
(2023) In Advanced Science 10(36).- Abstract
Protein dynamics have been investigated on a wide range of time scales. Nano- and picosecond dynamics have been assigned to local fluctuations, while slower dynamics have been attributed to larger conformational changes. However, it is largely unknown how fast (local) fluctuations can lead to slow global (allosteric) changes. Here, fast molecule-spanning dynamics on the 100 to 200 ns time scale in the heat shock protein 90 (Hsp90) are shown. Global real-space movements are assigned to dynamic modes on this time scale, which is possible by a combination of single-molecule fluorescence, quasi-elastic neutron scattering and all-atom molecular dynamics (MD) simulations. The time scale of these dynamic modes depends on the conformational... (More)
Protein dynamics have been investigated on a wide range of time scales. Nano- and picosecond dynamics have been assigned to local fluctuations, while slower dynamics have been attributed to larger conformational changes. However, it is largely unknown how fast (local) fluctuations can lead to slow global (allosteric) changes. Here, fast molecule-spanning dynamics on the 100 to 200 ns time scale in the heat shock protein 90 (Hsp90) are shown. Global real-space movements are assigned to dynamic modes on this time scale, which is possible by a combination of single-molecule fluorescence, quasi-elastic neutron scattering and all-atom molecular dynamics (MD) simulations. The time scale of these dynamic modes depends on the conformational state of the Hsp90 dimer. In addition, the dynamic modes are affected to various degrees by Sba1, a co-chaperone of Hsp90, depending on the location within Hsp90, which is in very good agreement with MD simulations. Altogether, this data is best described by fast molecule-spanning dynamics, which precede larger conformational changes in Hsp90 and might be the molecular basis for allostery. This integrative approach provides comprehensive insights into molecule-spanning dynamics on the nanosecond time scale for a multi-domain protein.
(Less)
- author
- organization
- publishing date
- 2023-12-27
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- heat shock protein 90, molecular dynamics simulations, neutron scattering, protein dynamics, single molecule fluorescence
- in
- Advanced Science
- volume
- 10
- issue
- 36
- article number
- 2304262
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:37984887
- scopus:85177222326
- ISSN
- 2198-3844
- DOI
- 10.1002/advs.202304262
- language
- English
- LU publication?
- yes
- id
- 21725680-b76c-4dcb-ab99-f781c64b80d2
- date added to LUP
- 2024-01-08 15:24:33
- date last changed
- 2024-04-23 11:00:58
@article{21725680-b76c-4dcb-ab99-f781c64b80d2,
abstract = {{<p>Protein dynamics have been investigated on a wide range of time scales. Nano- and picosecond dynamics have been assigned to local fluctuations, while slower dynamics have been attributed to larger conformational changes. However, it is largely unknown how fast (local) fluctuations can lead to slow global (allosteric) changes. Here, fast molecule-spanning dynamics on the 100 to 200 ns time scale in the heat shock protein 90 (Hsp90) are shown. Global real-space movements are assigned to dynamic modes on this time scale, which is possible by a combination of single-molecule fluorescence, quasi-elastic neutron scattering and all-atom molecular dynamics (MD) simulations. The time scale of these dynamic modes depends on the conformational state of the Hsp90 dimer. In addition, the dynamic modes are affected to various degrees by Sba1, a co-chaperone of Hsp90, depending on the location within Hsp90, which is in very good agreement with MD simulations. Altogether, this data is best described by fast molecule-spanning dynamics, which precede larger conformational changes in Hsp90 and might be the molecular basis for allostery. This integrative approach provides comprehensive insights into molecule-spanning dynamics on the nanosecond time scale for a multi-domain protein.</p>}},
author = {{Sohmen, Benedikt and Beck, Christian and Frank, Veronika and Seydel, Tilo and Hoffmann, Ingo and Hermann, Bianca and Nüesch, Mark and Grimaldo, Marco and Schreiber, Frank and Wolf, Steffen and Roosen-Runge, Felix and Hugel, Thorsten}},
issn = {{2198-3844}},
keywords = {{heat shock protein 90; molecular dynamics simulations; neutron scattering; protein dynamics; single molecule fluorescence}},
language = {{eng}},
month = {{12}},
number = {{36}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Advanced Science}},
title = {{The Onset of Molecule-Spanning Dynamics in Heat Shock Protein Hsp90}},
url = {{http://dx.doi.org/10.1002/advs.202304262}},
doi = {{10.1002/advs.202304262}},
volume = {{10}},
year = {{2023}},
}