Complete subunit architecture of the proteasome regulatory particle

By Gabriel Lander, Eric Estrin, M. Matyskiela, C. Bashore, E. Nogales, Andreas Martin. Nature, 2012

631 citations recorded by the source corpus.

The proteasome is the major ATP-dependent protease in eukaryotic cells, but limited structural information restricts a mechanistic understanding of its activities. The proteasome regulatory particle, consisting of the lid and base subcomplexes, recognizes and processes polyubiquitinated substrates. Here we used electron microscopy and a new heterologous expression system for the lid to delineate the complete subunit architecture of the regulatory particle from yeast. Our studies reveal the spatial arrangement of ubiquitin receptors, deubiquitinating enzymes and the protein unfolding machinery at subnanometre resolution, outlining the substrate’s path to degradation. Unexpectedly, the ATPase subunits within the base unfoldase are arranged in a spiral staircase, providing insight into potential mechanisms for substrate translocation through the central pore. Large conformational rearrangements of the lid upon holoenzyme formation suggest allosteric regulation of deubiquitination. We provide a structural basis for the ability of the proteasome to degrade a diverse set of substrates and thus regulate vital cellular processes.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6c19474e243afa73ca3b8ff3147028519fd28cc0

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Citations in the corpus

Structure and Function of the 26S Proteasome (2018, background): “Rpn11 resides just above the N-ring of the AAA+ motor and adjacent to the ubiquitin receptor Rpn10 (27, 123), in a location that is ideally suited for its key role in deubiquitination after the substrate is engaged, but before the AAA+ ATPase would unfold ubiquitin (Figures 5 and 6a).”
The Logic of the 26S Proteasome. (2017, positive): “The recent advances in single particle cryo-EM technology have made possible the near atomic resolution of the structures of yeast and human proteasomes, which certainly represents amajor achievement of the Baumeister (Beck et al., 2012; Wehmer et al., 2017) and Martin (Dambacher et al., 2016; Lande”
RELION: Implementation of a Bayesian approach to cryo-EM structure determination (2012, background): “see (Boettcher et al., 1997; Lau and Rubinstein, 2012; Lander et al., 2012), and recently several reconstructions to near-atomic resolution have been reported (Wolf et al.”
Go Hybrid: EM, Crystallography, and Beyond (2012, methodology): “com Two recent studies have combined cryoEM reconstructions of the 26S proteasome with biochemical data to provide a much more complete understanding of the RP architecture [22 ,23 ].”
Single-Particle Cryo-EM at Crystallographic Resolution. (2015, background): “…crystallography for studying such assemblies or complexes, such as clathrin coats (Fotin et al., 2004), the 26S proteasome (da Fonseca et al., 2012; Lander et al., 2012; Lasker et al., 2012), the anaphase promoting complex (Chang et al., 2014; da Fonseca et al., 2011), and chromatin fibers (Song…”
One number does not fit all: mapping local variations in resolution in cryo-EM reconstructions (2013, background): “In a study on the proteasome regulatory particle (Lander et al., 2012), the information derived from the local resolution analysis helped to delineate the boundaries of the subunits in the lid complex.”