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TitleComplete subunit architecture of the proteasome regulatory particle.
Journal, issue, pagesNature, Vol. 482, Issue 7384, Page 186-191, Year 2012
Publish dateJan 11, 2012
AuthorsGabriel C Lander / Eric Estrin / Mary E Matyskiela / Charlene Bashore / Eva Nogales / Andreas Martin /
PubMed AbstractThe 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, ...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.
External linksNature / PubMed:22237024 / PubMed Central
MethodsEM (single particle)
Resolution9.0 - 16.0 Å
Structure data

EMDB-1992:
The Saccharomyces cerevisiae 26S proteasome at subnanometer resolution
Method: EM (single particle) / Resolution: 9.0 Å

EMDB-1993:
Negative stain reconstruction of recombinantly expressed yeast proteasome lid
Method: EM (single particle) / Resolution: 16.0 Å

EMDB-1994:
Negative stain reconstruction of the Saccharomyces cerevisiae proteasome lid
Method: EM (single particle) / Resolution: 15.0 Å

Source
  • Saccharomyces cerevisiae (brewer's yeast)

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