Structural studies of HHARI/UbcH7∼Ub reveal unique E2∼Ub conformational restriction by RBR RING1
journal contributionposted on 12.08.2020, 11:44 by Katja K Dove, Jennifer L Olszewski, Luigi Martino, David M Duda, Xiaoli S Wu, Darcie J Miller, Katherine H Reiter, Katrin Rittinger, Brenda A Schulman, Rachel E Klevit
RING-between-RING (RBR) E3s contain RING1 domains that are structurally similar yet mechanistically distinct from canonical RING domains. Both types of E3 bind E2∼ubiquitin (E2∼Ub) via their RINGs but canonical RING E3s promote closed E2∼Ub conformations required for direct Ub transfer from the E2 to substrate, while RBR RING1s promote open E2∼Ub to favor Ub transfer to the E3 active site. This different RING/E2∼Ub conformation determines its direct target, which for canonical RING E3s is typically a substrate or substrate-linked Ub, but is the E3 active-site cysteine in the case of RBR-type E3s. Here we show that a short extension of HHARI RING1, namely Zn2+-loop II, not present in any RING E3s, acts as a steric wedge to disrupt closed E2∼Ub, providing a structural explanation for the distinctive RING1-dependent conformational restriction mechanism utilized by RBR E3s.
HHARIRBR E3 ligaseRING E3 ligaseUBAUBE2L3UbcH7ubiquitinubiquitin-conjugating enzymeBinding SitesCarrier ProteinsCatalytic DomainCrystallography, X-RayHumansModels, MolecularProtein ConformationProtein DomainsUbiquitinUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesZincRittinger FC001142Biophysics06 Biological Sciences08 Information and Computing Sciences03 Chemical Sciences