Nature communications, 2018-04, Vol.9 (1), p.1360-12, Article 1360
2018
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- Autor(en) / Beteiligte
- Titel
- Structural mechanism for nucleotide-driven remodeling of the AAA-ATPase unfoldase in the activated human 26S proteasome
- Ist Teil von
- Nature communications, 2018-04, Vol.9 (1), p.1360-12, Article 1360
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-018-03785-wTitel-ID: cdi_doaj_primary_oai_doaj_org_article_db4b804dc56b4cd2bb2a2dc1b71eeb2d
- Format
- –
- Schlagworte
- Adenosine triphosphatase, Adenosine Triphosphatases - chemistry, Adenosine Triphosphatases - genetics, Adenosine Triphosphatases - metabolism, Adenosine triphosphate, Adenosine Triphosphate - analogs & derivatives, Adenosine Triphosphate - chemistry, Adenosine Triphosphate - metabolism, Allosteric properties, Allosteric Regulation, Amino Acid Sequence, Arabidopsis Proteins - chemistry, Arabidopsis Proteins - genetics, Arabidopsis Proteins - metabolism, ATP, ATPases Associated with Diverse Cellular Activities - chemistry, ATPases Associated with Diverse Cellular Activities - genetics, ATPases Associated with Diverse Cellular Activities - metabolism, Binding Sites, Biology, Cancer, Cell division, Channel gating, Core particles, Cryoelectron Microscopy, Datasets, Gene expression, Holoenzymes - chemistry, Holoenzymes - genetics, Holoenzymes - metabolism, Humans, Kinetics, Models, Molecular, Nucleotides, Nucleotides - chemistry, Nucleotides - metabolism, Physics, Proteasome 26S, Proteasome Endopeptidase Complex - chemistry, Proteasome Endopeptidase Complex - genetics, Proteasome Endopeptidase Complex - metabolism, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Proteolysis, Saccharomyces cerevisiae Proteins - chemistry, Saccharomyces cerevisiae Proteins - genetics, Saccharomyces cerevisiae Proteins - metabolism, Sequence Alignment, Sequence Homology, Amino Acid, Substrates, Translocation