Structural Biology

Biography

Holger Stark has studied biochemistry and completed his PhD at the age of 29 years from the Free University Berlin, Germany. After a short postdoc at Imperial College in London (UK) he became a group leader at Marburg University (Germany) and moved from there to the Max-Planck-Institute in Goettingen (Germany) where he later became a director in 2015. He has over 100 publications and an H-index of 45.

Abstract

Single particle cryo electron microscopy (cryo-EM) has developed into a powerful technique to determine 3D structures of large macromolecular complexes. Due to improvements in instrumentation and computational image analysis, the number of high-resolution structures is steadily increasing. The method cannot only be used to determine high-resolution structures but also to study the dynamic behavior of macromolecular complexes and thus represents a very complementary method to X-ray crystallography. We have recently determined the structure of human proteasomes and their inhibition by anti-cancer drugs using X-ray crystallography to visualize the chemistry of inhibition at unprecedented resolution of 1.8 Å. By cryo-EM we were able to visualize the long-range allosteric conformational changes induced by the drug binding and visualized the effects of drug binding in terms of restrictions in the free-energy landscape of the human 26S proteasome. More examples of cryo-EM studies of dynamic processes in large macromolecular complexes will be presented at the conference.