5d0i

Publication Abstract from PubMed

RING-domain E3 ligases enhance transfer of ubiquitin to substrate proteins by stabilizing the RING-bound thioester-linked E2 approximately ubiquitin conjugate in a defined conformation that primes the active site for nucleophilic attack. Here we report that the monomeric RING domains from the human E3 ligases Arkadia and Ark2C bind directly to free ubiquitin with an affinity comparable to that of other dedicated ubiquitin-binding domains. Further work showed that the Ark-like RING domain and the noncovalently bound ubiquitin molecule coordinately stabilize the E2-conjugated ubiquitin (donor ubiquitin) in the 'closed' conformation. Our studies identify the RING domain of Arkadia as a ubiquitin-binding domain and provide insight into a new ubiquitin-dependent mechanism used by monomeric RING domains to activate ubiquitin transfer. This study also suggests how substrates that have been monoubiquitinated could be favored for further ubiquitination.

Secondary ubiquitin-RING docking enhances Arkadia and Ark2C E3 ligase activity.,Wright JD, Mace PD, Day CL Nat Struct Mol Biol. 2015 Dec 14. doi: 10.1038/nsmb.3142. PMID:26656854^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.