2018/04/04 by Yanan Zhu, Wei Li Wang, Daqi Yu +3 · 3 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · #AAA proteins #ATPase #Biochemistry #Biology #Cell biology #Chemistry #Endoplasmic Reticulum Stress and Disease #Enzyme #Gene #Genetics and Neurodevelopmental Disorders #Mechanism (biology) #Nucleotide #Physics #Proteasome #Ubiquitin and proteasome pathways
paper · pdf · doi:10.1038/s41467-018-03785-w
openalex publication_date 2018/04/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.