Biochemistry Seminar: R. Andrew Byrd, "Using NMR and dynamics to move beyond ground state structures"

ABSTRACT

Our laboratory has had a long-standing interest in molecular recognition and protein-protein interactions as they drive biological function. One system of interest is the post-translational modifications of proteins with ubiquitin and the regulation of proteins by proteosomal degradation. This pathway is involved in regulating vast segments of the proteome and requires the operation of three types of enzymes (E1, E2, E3) to build both characteristic chains of ubiquitin, for different biological signals, and to regulate different families and specific proteins as needed. The pathway relies on combinatorial action of these families of enzymes, and we have been interested in unraveling some of the interactions with aims to understand and achieve specificity. We have applied both NMR and crystallographic methods, as well as biophysical tools, to understand a particular mammalian E2:E3 pair of proteins associated with endoplasmic reticulum associated degradation (ERAD). The structural analyses have revealed allosteric mechanisms which are not simply understood by the structures. Recognizing that structures determined are representative of the ground state of each of the stages along the reaction pathway, we have been both applying and developing tools to reveal the conformational dynamics in this system. These results and the opportunities for examining a broad timescale of dynamics in complex biomolecular systems will be presented.