Toste Rêgo, A. and da Fonseca, P. C.A. (2019) Characterization of fully recombinant human 20S and 20S-PA200 proteasome complexes. Molecular Cell, 76(1), 138-147.e5. (doi: 10.1016/j.molcel.2019.07.014) (PMID:31473102) (PMCID:PMC6863390)
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Abstract
Proteasomes are essential in all eukaryotic cells. However, their function and regulation remain considerably elusive, particularly those of less abundant variants. We demonstrate the human 20S proteasome recombinant assembly and confirmed the recombinant complex integrity biochemically and with a 2.6 Å resolution cryo-EM map. To assess its competence to form higher-order assemblies, we prepared and analyzed recombinant human 20S-PA200, a poorly characterized nuclear complex. Its 3.0 Å resolution cryo-EM structure reveals the PA200 unique architecture; the details of its intricate interactions with the proteasome, resulting in unparalleled proteasome α ring rearrangements; and the molecular basis for PA200 allosteric modulation of the proteasome active sites. Non-protein cryo-EM densities could be assigned to PA200-bound inositol phosphates, and we speculate regarding their functional role. Here we open extensive opportunities to study the fundamental properties of the diverse and distinct eukaryotic proteasome variants and to improve proteasome targeting under different therapeutic conditions.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by Medical Research Council grant MC_UP_1201/5 (to P.C.A.d.F.) |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | da Fonseca, Professor Paula |
| Authors: | Toste Rêgo, A., and da Fonseca, P. C.A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | Molecular Cell |
| Publisher: | Elsevier |
| ISSN: | 1097-2765 |
| ISSN (Online): | 1097-4164 |
| Published Online: | 28 August 2019 |
| Copyright Holders: | Copyright © 2019 The Authors |
| First Published: | First published in Molecular Cell 76(1):138-147.e5 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
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