Colloquium: Fuzzy Structures: Single-Molecule Spectroscopy of Intrinsically Disordered Proteins



VU University Amsterdam, W&N-building, F-619, De Boelelaan 1081, Amsterdam

Fuzzy Structures: Single-Molecule Spectroscopy of Intrinsically Disordered Proteins

Claudiu Gradinaru, Department of Physics and Institute for Optical Sciences, University of Toronto, Canada

Raoul Frese




Fuzzy Structures: Single-Molecule Spectroscopyof Intrinsically Disordered Proteins

Intrinsically Disordered Proteins (IDPs) lack a stable tertiary folded structure under physiological conditions. Around 65% of the signaling and 75% of the human cancerassociated proteins have or are predicted to have significant disordered regions, thus implying a role for disorder in mediating regulatory protein interactions in complex biological processes. The question emerges of whether specific recognition can occur despite conformational disorder or whether disordered protein states may even provide advantages in recognition over well-folded proteins. With the ability to measure molecular processes without ensemble averaging, and to resolve the distribution of protein conformations, single-molecule fluorescence spectroscopy techniques are uniquely suited to study IDPs. In particular, we are interested on how electrostatics tweaks the conformational
properties of the disordered ensemble and how those are altered upon binding of IDPs to other proteins in the cell. In my talk, I will discuss how single-molecule techniques such as Förster Resonance Energy Transfer and Fluorescence Correlation Spectroscopy are currently implemented in my laboratory to investigate two IDP proteins: the cyclin inhibitor Sic1 from yeast and the SH3 domain of the Drosophila adapter protein Drk.

Claudiu Gradinaru