Paper Publications

Impact Factor:15.0

DOI number:10.1038/s41467-018-03785-w

Journal:Nat. Commun.

Abstract:The proteasome is a sophisticated ATP-dependent molecular machine responsible for protein degradation in all known eukaryotic cells. It remains elusive how conformational changes of the AAA-ATPase unfoldase in the regulatory particle (RP) control the gating of the substrate-translocation channel leading to the proteolytic chamber of the core particle (CP). Here we report three alternative states of the ATP-γ-S-bound human proteasome, in which the CP gates are asymmetrically open, visualized by cryo-EM at near-atomic resolutions. At least four nucleotides are bound to the AAA-ATPase ring in these open-gate states. Variation in nucleotide binding gives rise to an axial movement of the pore loops narrowing the substrate-translation channel, which exhibit remarkable structural transitions between the spiral-staircase and saddle-shaped-circle topologies. Gate opening in the CP is thus regulated by nucleotide-driven conformational changes of the AAA-ATPase unfoldase. These findings demonstrate an elegant mechanism of allosteric coordination among sub-machines within the human proteasome holoenzyme.

Indexed by:Journal paper

Discipline:Natural Science

Document Type:J

Volume:9

Issue:1

Page Number:1360

Translation or Not:no

Date of Publication:2018-04-10

Included Journals:SCI

First Author:Yanan Zhu,Wei Li Wang

Correspondence Author:Ying Lu,Youdong Mao

All the Authors:Daqi Yu,Qi Ouyang