Molecular Architecture and Assembly of the Eukaryotic Proteasome

Overview

Journal Annu Rev Biochem

Publisher Annual Reviews

Specialty Biochemistry

Date 2013 Mar 19

PMID 23495936

Citations 196

Authors

Robert J Tomko Jr

Mark Hochstrasser

Affiliations

Soon will be listed here.

Abstract

The eukaryotic ubiquitin-proteasome system is responsible for most aspects of regulatory and quality-control protein degradation in cells. Its substrates, which are usually modified by polymers of ubiquitin, are ultimately degraded by the 26S proteasome. This 2.6-MDa protein complex is separated into a barrel-shaped proteolytic 20S core particle (CP) of 28 subunits capped on one or both ends by a 19S regulatory particle (RP) comprising at least 19 subunits. The RP coordinates substrate recognition, removal of substrate polyubiquitin chains, and substrate unfolding and translocation into the CP for degradation. Although many atomic structures of the CP have been determined, the RP has resisted high-resolution analysis. Recently, however, a combination of cryo-electron microscopy, biochemical analysis, and crystal structure determination of several RP subunits has yielded a near-atomic-resolution view of much of the complex. Major new insights into chaperone-assisted proteasome assembly have also recently emerged. Here we review these novel findings.

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