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Crystal structure of a human Cdc34-ubiquitin thioester mimetic
Structural highlights
FunctionUB2R2_HUMAN Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes monoubiquitination and 'Lys-48'-linked polyubiquitination. May be involved in degradation of katenin.[1] [2] Publication Abstract from PubMedUbiquitin (Ub) signaling requires the sequential interactions and activities of three enzymes, E1, E2, and E3. Cdc34 is an E2 that plays a key role in regulating cell cycle progression and requires unique structural elements to function. The molecular basis by which Cdc34 engages its E1 and the structural mechanisms by which its unique C-terminal extension functions in Cdc34 activity are unknown. Here, we present crystal structures of Cdc34 alone and in complex with E1, and a Cdc34~Ub thioester mimetic that represents the product of Uba1-Cdc34 Ub transthiolation. These structures reveal conformational changes in Uba1 and Cdc34 and a unique binding mode that are required for transthiolation. The Cdc34~Ub structure reveals contacts between the Cdc34 C-terminal extension and Ub that stabilize Cdc34~Ub in a closed conformation and are critical for Ub discharge. Altogether, our structural, biochemical, and cell-based studies provide insights into the molecular mechanisms by which Cdc34 function in cells. Structural insights into E1 recognition and the ubiquitin-conjugating activity of the E2 enzyme Cdc34.,Williams KM, Qie S, Atkison JH, Salazar-Arango S, Alan Diehl J, Olsen SK Nat Commun. 2019 Jul 24;10(1):3296. doi: 10.1038/s41467-019-11061-8. PMID:31341161[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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