Deep classification of a large cryo-EM dataset defines the conformational landscape of the 26S proteasome
Abstract
The 26S proteasome is a multisubunit molecular machine for the targeted degradation of intracellular proteins. It has an essential role in the maintenance of protein homeostasis. During its functional cycle the proteasome undergoes large-scale conformational changes. For a detailed mechanistic understanding, an analysis of its conformational landscape is indispensable. Capitalizing on a very large dataset of more than 3 million individual particles and using a novel image-classification strategy, we have been able to deconvolute coexisting conformational states. This led to the discovery of conformation intermediates that provide deeper insights into the sequence of events following the initial binding of ubiquitylated substrates.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- April 2014
- DOI:
- 10.1073/pnas.1403409111
- Bibcode:
- 2014PNAS..111.5544U