8SE9
Cryo-EM structure of a double loaded human UBA7-UBE2L6-ISG15 thioester mimetic complex (Form 2)
Summary for 8SE9
| Entry DOI | 10.2210/pdb8se9/pdb |
| EMDB information | 40407 40408 40409 40410 40782 40799 |
| Descriptor | Ubiquitin-like modifier-activating enzyme 7, Ubiquitin-like protein ISG15, Ubiquitin/ISG15-conjugating enzyme E2 L6, ... (4 entities in total) |
| Functional Keywords | ligase, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 164140.10 |
| Authors | |
| Primary citation | Afsar, M.,Liu, G.,Jia, L.,Ruben, E.A.,Nayak, D.,Sayyad, Z.,Bury, P.D.S.,Cano, K.E.,Nayak, A.,Zhao, X.R.,Shukla, A.,Sung, P.,Wasmuth, E.V.,Gack, M.U.,Olsen, S.K. Cryo-EM structures of Uba7 reveal the molecular basis for ISG15 activation and E1-E2 thioester transfer. Nat Commun, 14:4786-4786, 2023 Cited by PubMed Abstract: 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. PubMed: 37553340DOI: 10.1038/s41467-023-39780-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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