Date: Tuesday, June 17, 2014
Time: 11:00 am
Speaker: Eva Nogales, UC Berkeley
Title: Visualization of biological macromolecular complexes by Cryo-EM
Location: 67-3111 Chemla Room
The molecular tasks required for the functioning of the cell are carried out by large molecular machines made of proteins or protein-nucleic acid complexes. Visualizing the structures of such complexes, especially in more than one functional state, is crucial for a mechanistic understanding of cellular function that can ultimately shed light on abnormal disease states and lead to therapeutic treatment. While X-ray crystallography can provide the structures of individual proteins or small complexes, crystallization precludes general applicability, especially when sample amounts are limited or when the complex exists in multiple biochemical and functional states. 3D cryo-electron microscopy (cryo-EM) single particle reconstruction is a technique ideally suited to visualize very large biological assemblies and has the potential to characterize conformational and biochemical heterogeneity. This methodology has just entered a new era with the introduction of direct electron-detection cameras (DEDCS) that are ideally suited to work in combination with high-end electron microscopes. As a result of this new technology, the structure of macromolecular complexes in solution (without naturally or artificially generated crystallographic packing) can now be produced at the previously unachievable resolution where individual amino acid side chains are well resolved. I will show examples from my own lab in the study of essential protein assemblies for the life of the cell.