6MSE

Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome

This is a non-PDB format compatible entry.

Summary for 6MSE

• Entry DOI: 10.2210/pdb6mse/pdb
• EMDB information: 9215 9216 9217 9218 9219 9220 9221 9222 9223 9224 9225 9226 9227 9228 9229
• Descriptor: 26S proteasome non-ATPase regulatory subunit 1, 26S proteasome non-ATPase regulatory subunit 8, 26S proteasome complex subunit SEM1, ... (38 entities in total)
• Functional Keywords: proteosome, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 48
• Total formula weight: 1673079.88

Authors

Mao, Y.D. (deposition date: 2018-10-16, release date: 2018-11-21, Last modification date: 2024-11-20)

Primary citation

Dong, Y.,Zhang, S.,Wu, Z.,Li, X.,Wang, W.L.,Zhu, Y.,Stoilova-McPhie, S.,Lu, Y.,Finley, D.,Mao, Y.
Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome.
Nature, 565:49-55, 2019

PubMed Abstract: The proteasome is an ATP-dependent, 2.5-megadalton molecular machine that is responsible for selective protein degradation in eukaryotic cells. Here we present cryo-electron microscopy structures of the substrate-engaged human proteasome in seven conformational states at 2.8-3.6 Å resolution, captured during breakdown of a polyubiquitylated protein. These structures illuminate a spatiotemporal continuum of dynamic substrate-proteasome interactions from ubiquitin recognition to substrate translocation, during which ATP hydrolysis sequentially navigates through all six ATPases. There are three principal modes of coordinated hydrolysis, featuring hydrolytic events in two oppositely positioned ATPases, in two adjacent ATPases and in one ATPase at a time. These hydrolytic modes regulate deubiquitylation, initiation of translocation and processive unfolding of substrates, respectively. Hydrolysis of ATP powers a hinge-like motion in each ATPase that regulates its substrate interaction. Synchronization of ATP binding, ADP release and ATP hydrolysis in three adjacent ATPases drives rigid-body rotations of substrate-bound ATPases that are propagated unidirectionally in the ATPase ring and unfold the substrate.

PubMed: 30479383
DOI: 10.1038/s41586-018-0736-4

Experimental method

ELECTRON MICROSCOPY (3.3 Å)