Structure of the proteasome activator REGα (PA28α)

J. R. Knowlton, S. C. Johnston, F. G. Whitby, C. Realini, Z. Zhang, M. Rechsteiner, C. P. Hill

Research output: Contribution to journalArticle

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Abstract

The specificity of the 20S proteasome, which degrades many intracellular proteins, is regulated by protein complexes that bind to one or both ends of the cylindrical proteasome structure. One of these regulatory complexes, the 11S regulator (known as REG or PA28), stimulates proteasome peptidase activity and enhances the production of antigenic peptides for presentation by class I molecules of the major histocompatibility complex (MHC). The three REG subunits that have been identified, REGα, REGβ and PEGγ (also known as the Ki antigen), share extensive sequence similarity, apart from a highly variable internal segment of 17-34 residues which may confer subunit-specific properties. REGα and REGβ preferentially form a heteromeric complex, although purified REGα forms a heptamer in solution and has biochemical properties similar to the heteromeric REGα/REGβ complex. We have now determined the crystal structure of human recombinant REGα at 2.8 Å resolution. The heptameric barrel-shaped assembly contains a central channel that has an opening of 20 Å diameter at one end and another of 30 Å diameter at the presumed proteasome-binding surface. The binding of REG probably causes conformational changes that open a pore in the proteasome α- subunits through which substrates and products can pass.

Original languageEnglish (US)
Pages (from-to)639-643
Number of pages5
JournalNature
Volume390
Issue number6660
DOIs
StatePublished - 1997
Externally publishedYes

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Proteasome Endopeptidase Complex
Major Histocompatibility Complex
Proteins
Peptide Hydrolases
Peptides

ASJC Scopus subject areas

  • General

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Knowlton, J. R., Johnston, S. C., Whitby, F. G., Realini, C., Zhang, Z., Rechsteiner, M., & Hill, C. P. (1997). Structure of the proteasome activator REGα (PA28α). Nature, 390(6660), 639-643. https://doi.org/10.1038/37670

Structure of the proteasome activator REGα (PA28α). / Knowlton, J. R.; Johnston, S. C.; Whitby, F. G.; Realini, C.; Zhang, Z.; Rechsteiner, M.; Hill, C. P.

In: Nature, Vol. 390, No. 6660, 1997, p. 639-643.

Research output: Contribution to journalArticle

Knowlton, JR, Johnston, SC, Whitby, FG, Realini, C, Zhang, Z, Rechsteiner, M & Hill, CP 1997, 'Structure of the proteasome activator REGα (PA28α)', Nature, vol. 390, no. 6660, pp. 639-643. https://doi.org/10.1038/37670
Knowlton JR, Johnston SC, Whitby FG, Realini C, Zhang Z, Rechsteiner M et al. Structure of the proteasome activator REGα (PA28α). Nature. 1997;390(6660):639-643. https://doi.org/10.1038/37670
Knowlton, J. R. ; Johnston, S. C. ; Whitby, F. G. ; Realini, C. ; Zhang, Z. ; Rechsteiner, M. ; Hill, C. P. / Structure of the proteasome activator REGα (PA28α). In: Nature. 1997 ; Vol. 390, No. 6660. pp. 639-643.
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