Metastable Mesoscopic Clusters: a Novel Class of Protein Aggregates

Spring 2017
Speaker: 
Peter Vekilov
Affiliation: 
University of Houston
Wed, 2017-03-15
3:00PM
487 GWC
Host: 
Dmitry Matyushov

Abstract

Protein-rich clusters of steady submicron size and narrow size distribution exist in protein solutions in apparent violation of the classical laws of phase equilibrium.  Even though they contain a minor fraction of the total protein, recent evidence indicates that they may serve as essential precursors for the nucleation of ordered solids such as crystals, sickle-cell hemoglobin polymers, and amyloid fibrils.  The cluster formation mechanism remains elusive.  We use the proteins that differ in their structural and chemical properties and explore the response of cluster populations to the electrostatic forces, which govern numerous biophysical phenomena, including crystallization and fibrillization.  We tune the strength of intermolecular electrostatic forces by varying the solution ionic strength I and pH and find that despite the weaker repulsion at higher I and pH, the cluster size remains constant.  Cluster responses to the presence of urea and ethanol demonstrate that cluster formation is controlled by hydrophobic interactions between the peptide backbones, exposed to the solvent after partial protein unfolding that may lead to transient protein oligomers.  These findings reveal that the mechanism of the mesoscopic clusters is fundamentally different from those underlying the two main classes of ordered protein solid phases, crystals and amyloid fibrils, and partial unfolding of the protein chain may play a significant role.

    

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