  Protein dynamics has 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 local fluctuations can lead to global allosteric changes.
Here we show that molecule-spanning dynamics on the 100 ns time scale precede
larger allosteric changes. We assign global real-space movements to dynamic
modes on the 100 ns time scales, which became possible by a combination of
single-molecule fluorescence, quasi-elastic neutron scattering and all-atom MD
simulations. Additionally, we demonstrate the effect of Sba1, a co-chaperone of
Hsp90, on these molecule-spanning dynamics, which implies functional importance
of such dynamics. Our integrative approach provides comprehensive insights into
molecule-spanning dynamics on the nanosecond time scale for a multi-domain
protein and indicates that such dynamics are the molecular basis for allostery
and large conformational changes in proteins.
