BIO seminar: Single-Molecule Spectroscopy of a Highly Disordered Protein Complex
From Dynamics and Kinetics to Function and Thermodynamics
Speaker: Dr. Ben Schuler, Department of Biochemistry and Physics, University of Zurich, Switzerland
Host: Birthe Kragelund, Section for Biomolecular Sciences
The functions of proteins have traditionally been linked to their well-defined three-dimensional, folded structures. However, it is now clear that many proteins perform essential functions without being folded. A versatile way of investigating such intrinsically disordered proteins (IDPs) and their interactions is the integration of single-molecule FRET spectroscopy with other biophysical methods and molecular simulations.
I will illustrate this approach in the context of a remarkable interaction mechanism: Two intrinsically disordered and highly charged human proteins, histone H1 and its nuclear chaperone prothymosin α, associate with picomolar affinity, but they fully retain their structural disorder, long-range flexibility, and highly dynamic character when bound to each other.
We have obtained an increasingly detailed understanding of the architecture and dynamics of this complex, the kinetic mechanisms enabled by disorder, its unusual thermodynamic properties, and the potential consequences for cellular regulation.