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TitleAllosteric regulation of the 20S proteasome by the Catalytic Core Regulators (CCRs) family.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 3126, Year 2023
Publish dateMay 30, 2023
AuthorsFanindra Kumar Deshmukh / Gili Ben-Nissan / Maya A Olshina / Maria G Füzesi-Levi / Caley Polkinghorn / Galina Arkind / Yegor Leushkin / Irit Fainer / Sarel J Fleishman / Dan Tawfik / Michal Sharon /
PubMed AbstractControlled degradation of proteins is necessary for ensuring their abundance and sustaining a healthy and accurately functioning proteome. One of the degradation routes involves the uncapped 20S ...Controlled degradation of proteins is necessary for ensuring their abundance and sustaining a healthy and accurately functioning proteome. One of the degradation routes involves the uncapped 20S proteasome, which cleaves proteins with a partially unfolded region, including those that are damaged or contain intrinsically disordered regions. This degradation route is tightly controlled by a recently discovered family of proteins named Catalytic Core Regulators (CCRs). Here, we show that CCRs function through an allosteric mechanism, coupling the physical binding of the PSMB4 β-subunit with attenuation of the complex's three proteolytic activities. In addition, by dissecting the structural properties that are required for CCR-like function, we could recapitulate this activity using a designed protein that is half the size of natural CCRs. These data uncover an allosteric path that does not involve the proteasome's enzymatic subunits but rather propagates through the non-catalytic subunit PSMB4. This way of 20S proteasome-specific attenuation opens avenues for decoupling the 20S and 26S proteasome degradation pathways as well as for developing selective 20S proteasome inhibitors.
External linksNat Commun / PubMed:37253751 / PubMed Central
MethodsEM (single particle)
Resolution12.0 Å
Structure data

EMDB-17118: 20S proteasome & CBR3 complex
Method: EM (single particle) / Resolution: 12.0 Å

Source
  • Rattus norvegicus (Norway rat)
  • Homo sapiens (human)

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