Mechanism-Dependent Modulation of Ultrafast Interfacial Water Dynamics in Intrinsically Disordered Protein Complexes

Area of Science:

• Biochemistry
• Structural Biology
• Biophysics

Background:

• Intrinsically disordered proteins (IDPs) lack stable structures, making their recognition dynamics-dependent.
• IDPs are crucial in cellular processes, including nucleocytoplasmic transport.
• Understanding IDP dynamics is key to elucidating molecular recognition mechanisms.

Purpose of the Study:

• To investigate the interplay between protein dynamics and molecular recognition in IDPs.
• To examine conformational and solvent dynamics in IDPs upon partner binding.
• To compare binding mechanisms of two IDPs, IBB and Nup153FG, with Importinβ.

Main Methods:

• Utilized time-resolved spectroscopic techniques (femtosecond to nanosecond timescales).
• Studied conformational dynamics of IBB and Nup153FG.
• Analyzed surface water dynamics and its changes upon binding to Importinβ.

Main Results:

• Observed distinct binding mechanisms for IBB (coupled folding-binding) and Nup153FG (fuzzy complex) with Importinβ.
• Found unperturbed or accelerated water dynamics in the Nup153FG-Importinβ fuzzy complex interface.
• Detected a significant slowdown of water dynamics in the more rigid IBB-Importinβ complex interface.

Conclusions:

• Interfacial water dynamics correlate with the plasticity of IDP-protein complexes.
• Differential modulation of water dynamics has functional implications in cellular processes.
• Findings provide insights into the role of dynamics in nucleocytoplasmic transport mediated by IDPs.