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Article Dans Une Revue Advanced Science Année : 2023

The Onset of Molecule‐Spanning Dynamics in Heat Shock Protein Hsp90

Benedikt Sohmen
Christian Beck
Veronika Frank
Tilo Seydel
Ingo Hoffmann
Bianca Hermann
Mark Nüesch
Marco Grimaldo
Frank Schreiber
Steffen Wolf
Felix Roosen‐runge
Thorsten Hugel

Résumé

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.

Dates et versions

hal-04347531 , version 1 (15-12-2023)

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Citer

Benedikt Sohmen, Christian Beck, Veronika Frank, Tilo Seydel, Ingo Hoffmann, et al.. The Onset of Molecule‐Spanning Dynamics in Heat Shock Protein Hsp90. Advanced Science, 2023, ⟨10.1002/advs.202304262⟩. ⟨hal-04347531⟩
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