University of Southern California
Ray R. Irani Hall
Molecular and Computational Biology
Computational Biology Colloquium
Carlos Camacho
Department of Computational and Systems Biology
University of Pittsburgh
"On the Origin of Disordered Proteins
and their Function"
Abstract:
A large number of proteins are sufficiently unstable that their full 3D structure cannot be resolved. The origins of this intrinsic disorder are not well understood, but its ubiquitous presence undercuts the principle that a protein’s structure determines its function. My seminar will present a thermodynamic theory that makes quantitative predictions regarding the role of intrinsic disorder in protein structure and function. Predictions are validated based on genome-wide surveys of both the amount of disorder for different functional categories and binding affinities for both prokaryotic and eukaryotic genomes. Without assuming any a priori structure–function relationship, we demonstrate that enzymes and low-affinity binding proteins prefer ordered structures, whereas only high-affinity binding proteins (found mostly in eukaryotes) can tolerate disorder. Relevant to both transcription and signal transduction, the theory also explains how increasing disorder can tune the binding affinity to maximize the specificity of promiscuous interactions. Finally, I will describe the compatibility of these fundamental physical principles with the molecular basis of disordered peptides binding to PDZ domains.
WEDNESDAY, May 5, 2010
2:00 pm
RRI 101
