4KBL

Structure of HHARI, a RING-IBR-RING ubiquitin ligase: autoinhibition of an Ariadne-family E3 and insights into ligation mechanism

Summary for 4KBL

• Entry DOI: 10.2210/pdb4kbl/pdb
• Related: 4KC9
• Descriptor: E3 ubiquitin-protein ligase ARIH1, ZINC ION (2 entities in total)
• Functional Keywords: ring-ibr-ring, e3 ubiquitin ligase, ligase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q9Y4X5
• Total number of polymer chains: 2
• Total formula weight: 129468.71

Authors

Duda, D.M.,Olszewski, J.L.,Schulman, B.A. (deposition date: 2013-04-23, release date: 2013-05-29, Last modification date: 2024-02-28)

Primary citation

Duda, D.M.,Olszewski, J.L.,Schuermann, J.P.,Kurinov, I.,Miller, D.J.,Nourse, A.,Alpi, A.F.,Schulman, B.A.
Structure of HHARI, a RING-IBR-RING Ubiquitin Ligase: Autoinhibition of an Ariadne-Family E3 and Insights into Ligation Mechanism.
Structure, 21:1030-1041, 2013

PubMed Abstract: A distinct mechanism for ubiquitin (Ub) ligation has recently been proposed for the RING1-IBR-RING2 (RBR) family of E3s: an N-terminal RING1 domain recruits a thioester-linked intermediate complex between Ub and the E2 UbcH7, and a structurally distinct C-terminal RING2 domain displays a catalytic cysteine required for Ub ligation. To obtain insights into RBR E3s, we determined the crystal structure of the human homolog of Ariadne (HHARI), which reveals the individual RING1, IBR, and RING2 domains embedded in superdomains involving sequences specific to the Ariadne RBR subfamily. The central IBR is flanked on one side by RING1, which is exposed and binds UbcH7. On the other side, a C-terminal autoinhibitory "Ariadne domain" masks the RING2 active site. Insights into RBR E3 mechanisms are provided by structure-based mutations that indicate distinct steps of relief from autoinhibition, Ub transfer from E2 to HHARI, and ligation from the HHARI cysteine to a terminal acceptor.

PubMed: 23707686
DOI: 10.1016/j.str.2013.04.019

Experimental method

X-RAY DIFFRACTION (3.3 Å)