Molecular Model of the Human 26S Proteasome

Division of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, UK.
Molecular cell (Impact Factor: 14.02). 04/2012; 46(1):54-66. DOI: 10.1016/j.molcel.2012.03.026
Source: PubMed


The 26S proteasome plays a fundamental role in eukaryotic homeostasis by undertaking the highly controlled degradation of a wide range of proteins, including key cellular regulators such as those controlling cell-cycle progression and apoptosis. Here we report the structure of the human 26S proteasome determined by cryo-electron microscopy and single-particle analysis, with secondary structure elements identified both in the 20S proteolytic core region and in the 19S regulatory particle. We have used this information together with crystal structures, homology models, and other biochemical information to construct a molecular model of the complete 26S proteasome. This model allows for a detailed description of the 20S core within the 26S proteasome and redefines the overall assignment of subunits within the 19S regulatory particle. The information presented here provides a strong basis for a mechanistic understanding of the 26S proteasome.

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    • "Structurally, the PCI-containing subunits arrange in a horseshoe-like shape, juxtaposed with the two MPN subunits. This architecture is strikingly similar to that of the 26S proteasome lid and the eukaryotic translation initiation factor eIF3 [8], [9], [10], [11], [12], [13]. "
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    • "This was in according with the expression pattern of Ac larvae fed with RJM. 26S proteasome (Rpn9) plays a fundamental role in eukaryotic homeostasis [71], [72]. The ubiquitin-proteasome system mediated viral protein degradation constitutes a host defense process against some RNA viral infections [73]. "
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    • "How the highly related Rpt subunits assemble with their cognate partner in the complex cellular environment remains to be elucidated. Since Adc17 binds to the amino-terminal region of Rpt6, and since structural analyses of the proteasome have revealed that Rpt dimers are held together by the amino-terminal regions of each Rpt (Beck et al., 2012; da Fonseca et al., 2012; Lander et al., 2012), we wondered whether Adc17 played a role in the Rpt6- Rpt3 heterodimer formation. We therefore designed assays to test this possibility. "
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