7OD1
Crystal structure of RBR ubiquitin ligase ARIH2
Summary for 7OD1
Entry DOI | 10.2210/pdb7od1/pdb |
Descriptor | E3 ubiquitin-protein ligase ARIH2, ZINC ION (3 entities in total) |
Functional Keywords | triad1, arih2, rbr, ubiquitin, e3 ligase, ligase |
Biological source | Homo sapiens (Human) |
Total number of polymer chains | 2 |
Total formula weight | 116572.60 |
Authors | Kostrhon, S.P.,Prabu, J.R.,Schulman, B.A. (deposition date: 2021-04-28, release date: 2021-09-15, Last modification date: 2024-06-19) |
Primary citation | Kostrhon, S.,Prabu, J.R.,Baek, K.,Horn-Ghetko, D.,von Gronau, S.,Klugel, M.,Basquin, J.,Alpi, A.F.,Schulman, B.A. CUL5-ARIH2 E3-E3 ubiquitin ligase structure reveals cullin-specific NEDD8 activation. Nat.Chem.Biol., 17:1075-1083, 2021 Cited by PubMed Abstract: An emerging mechanism of ubiquitylation involves partnering of two distinct E3 ligases. In the best-characterized E3-E3 pathways, ARIH-family RING-between-RING (RBR) E3s ligate ubiquitin to substrates of neddylated cullin-RING E3s. The E3 ARIH2 has been implicated in ubiquitylation of substrates of neddylated CUL5-RBX2-based E3s, including APOBEC3-family substrates of the host E3 hijacked by HIV-1 virion infectivity factor (Vif). However, the structural mechanisms remained elusive. Here structural and biochemical analyses reveal distinctive ARIH2 autoinhibition, and activation on assembly with neddylated CUL5-RBX2. Comparison to structures of E3-E3 assemblies comprising ARIH1 and neddylated CUL1-RBX1-based E3s shows cullin-specific regulation by NEDD8. Whereas CUL1-linked NEDD8 directly recruits ARIH1, CUL5-linked NEDD8 does not bind ARIH2. Instead, the data reveal an allosteric mechanism. NEDD8 uniquely contacts covalently linked CUL5, and elicits structural rearrangements that unveil cryptic ARIH2-binding sites. The data reveal how a ubiquitin-like protein induces protein-protein interactions indirectly, through allostery. Allosteric specificity of ubiquitin-like protein modifications may offer opportunities for therapeutic targeting. PubMed: 34518685DOI: 10.1038/s41589-021-00858-8 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.45 Å) |
Structure validation
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