Structural Biology/Biochemistry Seminar
11:15 am – 12:30 pm | 112 KLB
Tuesday March 3, 2015
“Cryo-EM of Helical Polymers at Near-Atomic Resolution Gives New Insights Into Evolutionary Conservation and Divergence”
Many proteins assemble either naturally or pathologically into helical polymers, but structural information about these assemblies has been very difficult to obtain as almost none of these proteins can be crystallized in their polymeric state. With the introduction of direct electron detectors the field of cryo-EM is on the verge of a major revolution, and near-atomic and atomic resolution can now be routinely obtained for many such filamentous assemblies. We have been looking at a number of different polymer families, from bacterial pili to eukaryotic actin, and show the new insights that emerge with this high resolution. In particular, we can demonstrate in an in vitro system the lability of quaternary structure, which is the change in the helical structure introduced by small changes in amino acid sequence. We postulate that this is a mechanism for the amplification of sequence differences leading to evolutionary divergence. We also can use our near-atomic resolution to answer the question of why every amino acid in actin has been under intense selective pressure for hundreds of millions of years.
Dr. Edward Egelman
Professor, Dept. of Biochemistry and Molecular Genetics
University of Virginia
President-Elect, Biophysical Society
Lab Research Interests: We are interested in protein-protein and protein-DNA complexes. The main tools that we employ are electron microscopy and computational image analysis. Our long-standing interests have involved F-actin and RecA/Rad51 recombination filaments. However, our development of new methods for the analysis and reconstruction of helical polymers has led us more recently to apply these tools to bacterial pili, Type Three Secretion System components, and filamentous bacteriophage.