Physics Colloquium: Mapping Conformations and Folding Dynamics in Unstructured Proteins at the Single-Molecule Level

Event Details

  • Speaker(s): Dr. Claudiu Gradinaru
  • Date:
  • Time: 2:30 PM
  • Location: SCIE 1511

Abstract

Intrinsically disordered proteins (IDPs) lack stable globular tertiary folded structure under physio-logical conditions. Roughly 65% of the signaling and 75% of the human cancer-associated proteins are predicted to have significant disordered regions, thus implying a role for disorder in mediating regulatory protein interactions in complex biological processes. An interesting 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.
Single-molecule experiments record molecular events without ensemble averaging, and offer a unique view of microscopic conformations and interaction dynamics in a complex biological system. Single-molecule fluorescence spectroscopy applied to the study of IDPs provides important new in-sights into the conformational properties of the disordered ensemble and how these features are al-tered by solution properties (ionic strength, pH, osmolytes) and by binding to other proteins. In my talk, I will discuss how single-molecule techniques such as Förster Resonance Energy Transfer (FRET) and Fluorescence Correlation Spectroscopy (FCS) are currently employed in my lab to in-vestigate two such proteins, the cyclin inhibitor Sic1 from yeast and the SH3 domain of the Drosophi-la adapter protein Drk.

Intrinsically disordered proteins (IDPs) lack stable globular tertiary folded structure under physio-logical conditions. Roughly 65% of the signaling and 75% of the human cancer-associated proteins are predicted to have significant disordered regions, thus implying a role for disorder in mediating regulatory protein interactions in complex biological processes. An interesting 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.Single-molecule experiments record molecular events without ensemble averaging, and offer a unique view of microscopic conformations and interaction dynamics in a complex biological system. Single-molecule fluorescence spectroscopy applied to the study of IDPs provides important new in-sights into the conformational properties of the disordered ensemble and how these features are al-tered by solution properties (ionic strength, pH, osmolytes) and by binding to other proteins. In my talk, I will discuss how single-molecule techniques such as Förster Resonance Energy Transfer (FRET) and Fluorescence Correlation Spectroscopy (FCS) are currently employed in my lab to in-vestigate two such proteins, the cyclin inhibitor Sic1 from yeast and the SH3 domain of the Drosophi-la adapter protein Drk.

Host:   Dr. John Dutcher