Progress in Structural Biology of 26S Proteasome

Abstract

26S proteasome is the major molecular machine that is responsible for protein degradation in eukaryotic cells. By specifically eliminating target proteins, it is involved in almost every life activities of organisms. 26S proteasome consists of 47 protein members, and can be divided into 19S regulatory particle and 20S core particle. The target protein substrate with polyubiquitin-tag was firstly recognized by 19S regulatory particle, and then unfolded and translocated into 20S core particle for degradation. Due to the structural composition complexity and huge molecular weight of 26S proteasome, the complete structure cannot be resolved with the current X-ray and NMR technology. Only crystal structures of some single subunits and small subcomplex are resolved so far. Yet Cryo-EM technology is under primary developing period in rather a long time. The efforts towards the 3D structure reconstitution of 26S proteasome were not effective. In the past few years, along with experience accumulation in large molecular complexes structure resolved by X-ray, and technical revolution in Cryo-EM field, the 3D structure reconstitution of the complete 26S proteasome moves into a new promising stage. This manuscript reviews the recent important progress in structural biology of 26S proteasome and prospects the development and challenge in the future.