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7OD1

Crystal structure of RBR ubiquitin ligase ARIH2

Summary for 7OD1
Entry DOI10.2210/pdb7od1/pdb
DescriptorE3 ubiquitin-protein ligase ARIH2, ZINC ION (3 entities in total)
Functional Keywordstriad1, arih2, rbr, ubiquitin, e3 ligase, ligase
Biological sourceHomo sapiens (Human)
Total number of polymer chains2
Total formula weight116572.60
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 citationKostrhon, 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: 34518685
DOI: 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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건을2024-11-06부터공개중

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