4auq

Publication Abstract from PubMed

Certain RING ubiquitin ligases (E3s) dimerize to facilitate ubiquitin (Ub) transfer from ubiquitin-conjugating enzyme (E2) to substrate, but structural evidence on how this process promotes Ub transfer is lacking. Here we report the structure of the human dimeric RING domain from BIRC7 in complex with the E2 UbcH5B covalently linked to Ub (UbcH5B approximately Ub). The structure reveals extensive noncovalent donor Ub interactions with UbcH5B and both subunits of the RING domain dimer that stabilize the globular body and C-terminal tail of Ub. Mutations that disrupt these noncovalent interactions or RING dimerization reduce UbcH5B approximately Ub binding affinity and ubiquitination activity. Moreover, NMR analyses demonstrate that BIRC7 binding to UbcH5B approximately Ub induces peak-shift perturbations in the donor Ub consistent with the crystallographically-observed Ub interactions. Our results provide structural insights into how dimeric RING E3s recruit E2 approximately Ub and optimize the donor Ub configuration for transfer.

BIRC7-E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer.,Dou H, Buetow L, Sibbet GJ, Cameron K, Huang DT Nat Struct Mol Biol. 2012 Sep;19(9):876-83. doi: 10.1038/nsmb.2379. Epub 2012 Aug, 14. PMID:22902369^[1]

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