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bioRxiv · 10.1101/132613

Nucleotide-Driven Triple-State Remodeling Of The AAA-ATPase Channel In The Activated Human 26S Proteasome

Zhu, Y.·Wang, W. L.·Yu, D.·Ouyang, Q.·Lu, Y.·Mao, Y.
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Abstract

The proteasome is a sophisticated ATP-dependent molecular machine responsible for protein degradation in all eukaryotic cells. It remains elusive how conformational changes of the AAA-ATPase unfoldase in the regulatory particle (RP) control the gating of substrate-translocation channel to the proteolytic chamber of the core particle (CP). Here we report three alternative states of the ATP-{gamma}S-bound human proteasome, in which the CP gate is asymmetrically open, visualized by cryo-EM at near-atomic resolutions. Only four nucleotides are stably bound to the AAA-ATPase ring in the open-gate states. Concerted nucleotide exchange gives rise to a back-and-forth wobbling motion of the AAA-ATPase channel, coincident with remarkable transitions of their pore loops between the spiral staircase and saddle-shaped circle topologies. Gate opening in the CP is thus controlled with nucleotide-driven remodeling of the AAA-ATPase unfoldase. These findings demonstrate an elegant mechanism of allosteric coordination among sub-machines within the holoenzyme that is crucial for substrate translocation.

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Zhu, Y., Wang, W. L., Yu, D., Ouyang, Q., Lu, Y., Mao, Y.. 2017-05-01. Nucleotide-Driven Triple-State Remodeling Of The AAA-ATPase Channel In The Activated Human 26S Proteasome. https://doi.org/10.1101/132613

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