5VFO

Nucleotide-driven Triple-state Remodeling of the AAA-ATPase Channel in the Activated Human 26S Proteasome

Summary for 5VFO

• Entry DOI: 10.2210/pdb5vfo/pdb
• Related: 5VFP 5VFQ 5VFR 5VFS 5VFT 5VFU
• EMDB information: 8662 8663 8664 8665 8666 8667 8668
• Descriptor: Proteasome subunit alpha type-6, Proteasome subunit beta type-3, Proteasome subunit beta type-2, ... (14 entities in total)
• Functional Keywords: 26s proteasome, atp-dependent protease, aaa-atpase, peptide-unfolding channel, 20s core particle, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 28
• Total formula weight: 694178.77

Authors

Zhu, Y.,Wang, W.L.,Yu, D.,Ouyang, Q.,Lu, Y.,Mao, Y. (deposition date: 2017-04-08, release date: 2018-07-18)

Primary citation

Zhu, Y.,Wang, W.L.,Yu, D.,Ouyang, Q.,Lu, Y.,Mao, Y.
Structural mechanism for nucleotide-driven remodeling of the AAA-ATPase unfoldase in the activated human 26S proteasome.
Nat Commun, 9:1360-1360, 2018

PubMed 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.

PubMed: 29636472
DOI: 10.1038/s41467-018-03785-w

Experimental method

ELECTRON MICROSCOPY (3.5 Å)