Deep Mutagenesis Analysis of Evolvability in a DNA Polymerase AAA+ Clamp Loader System

(This will be a hybrid lecture, in person at Lipsett Amphitheather and on NIH VideoCast.)  Dr. Kuriyan’s research concerns the atomic-level structure and mechanism of the enzymes and molecular switches that carry out cellular signal transduction. His laboratory uses x-ray crystallography to determine the three-dimensional structures of proteins involved in signaling, as well as biochemical, biophysical, and cell biological analyses to elucidate mechanisms. Breakthroughs from the lab have included determining the auto-inhibited structures of several tyrosine kinases, including Src family kinases and elucidating the mechanism of allosteric activation of the kinase domains of the EGF receptor. His laboratory has provided a fundamental understanding of the structure and regulation several other signaling proteins, including STATs, the Ras activator SOS, and calcium/calmodulin-dependent protein kinase-II. Their structural insights have helped understand how the misregulation of these enzymes is often coupled to cancer and immune diseases and has implications for the development of kinase-targeted drugs to treat these diseases. His lab has also made fundamental contributions to understanding the structural basis for high-speed DNA replication.