Edward Gogol   ASSOCIATE PROFESSOR, CBB IPHD DOCTORAL FACULTY

Ph.D. Yale University

Edward Gogol
   415 BSB
    235-2584
Research Areas

The activities of cellular proteins are determined not only by levels of gene transcription and translation, but also by rates of protein folding and degradation. These processes are promoted by two molecular machines, chaperonins and proteasomes, which play major roles in determining levels of intracellular proteins. Failure to properly regulate these crucial cell components leads to breakdown of cellular homeostatis, and is thought to be a major component of many degenerative diseases. We use direct structural visualization of these macromolecular complexes in functionally-defined states by cryo-electron microscopy, and subsequent computer-aided analysis of the images obtained, to understand the basis of their action and regulation. Our work has shown that the proteasome is activated by a cooperative binding of a regulatory complex, PA700, to either end of the symmetrical assembly. We are currently exploring the mechanism of this activation, as well as the basis for its inhibition. A more recent project in the lab aims at understanding the steps involved in the mechanism of protein folding catalyzed by the E. coli chaperonin, GroEL. Using three-dimensional reconstruction of cryoEM images, we have visualized conformational changes in GroEL induced by binding a denatured substrate protein, suggesting the nature of early events in protein folding by the chaperonin.