Author:
Liebau Jobst,Lazzaretti Daniela,Bichler Anna,Pilsl Michael,Sprangers Remco
Abstract
AbstractMolecular machines play pivotal roles in all biological processes. Most structural methods, however, are unable to directly probe molecular motions. We demonstrate that dedicated NMR experiments can provide quantitative insights into functionally important dynamic regions in very large asymmetric protein complexes. We establish this for the 410 kDa eukaryotic RNA exosome complex that contains ten distinct protein chains. NMR data reveal site-specific interactions and conformational changes in regions that are invisible in static cryo-EM and crystal structures. In particular, we identify a flexible plug region that blocks an aberrant route of the RNA to the active site. Our work thus demonstrates that a combination of state-of-the-art structural biology methods can provide quantitative insights into molecular machines that go well beyond static images.
Publisher
Cold Spring Harbor Laboratory