8seb | pdb_00008seb

Cryo-EM structure of a single loaded human UBA7-UBE2L6-ISG15 adenylate complex

spinqualitylabelsall models 8seb, resolution 3.24Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8seb is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.24Å Ligands: AMP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function UBA7_HUMAN Activates ubiquitin by first adenylating with ATP its C-terminal glycine residue and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Catalyzes the ISGylation of influenza A virus NS1 protein. Publication Abstract from PubMed ISG15 plays a crucial role in the innate immune response and has been well-studied due to its antiviral activity and regulation of signal transduction, apoptosis, and autophagy. ISG15 is a ubiquitin-like protein that is activated by an E1 enzyme (Uba7) and transferred to a cognate E2 enzyme (UBE2L6) to form a UBE2L6-ISG15 intermediate that functions with E3 ligases that catalyze conjugation of ISG15 to target proteins. Despite its biological importance, the molecular basis by which Uba7 catalyzes ISG15 activation and transfer to UBE2L6 is unknown as there is no available structure of Uba7. Here, we present cryo-EM structures of human Uba7 in complex with UBE2L6, ISG15 adenylate, and ISG15 thioester intermediate that are poised for catalysis of Uba7-UBE2L6-ISG15 thioester transfer. Our structures reveal a unique overall architecture of the complex compared to structures from the ubiquitin conjugation pathway, particularly with respect to the location of ISG15 thioester intermediate. Our structures also illuminate the molecular basis for Uba7 activities and for its exquisite specificity for ISG15 and UBE2L6. Altogether, our structural, biochemical, and human cell-based data provide significant insights into the functions of Uba7, UBE2L6, and ISG15 in cells. Cryo-EM structures of Uba7 reveal the molecular basis for ISG15 activation and E1-E2 thioester transfer.,Afsar M, Liu G, Jia L, Ruben EA, Nayak D, Sayyad Z, Bury PDS, Cano KE, Nayak A, Zhao XR, Shukla A, Sung P, Wasmuth EV, Gack MU, Olsen SK Nat Commun. 2023 Aug 8;14(1):4786. doi: 10.1038/s41467-023-39780-z. PMID:37553340 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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