The onset of molecule-spanning dynamics in a multi-domain protein

TL;DR

This study reveals that nanosecond-scale molecule-spanning dynamics in a multi-domain protein precede and potentially facilitate larger allosteric and conformational changes, highlighting their functional significance.

Contribution

It introduces an integrative approach combining fluorescence, neutron scattering, and MD simulations to characterize nanosecond dynamics linked to allostery in proteins.

Findings

Molecule-spanning dynamics occur on the 100 ns time scale.

These dynamics precede larger conformational changes.

Sba1 modulates these dynamics, indicating functional relevance.

Abstract

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.