8oif

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== Function ==
== Function ==
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[https://www.uniprot.org/uniprot/UBA7_HUMAN 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.<ref>PMID:16254333</ref> <ref>PMID:20133869</ref>
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[https://www.uniprot.org/uniprot/UBA7_HUMAN UBA7_HUMAN] E1-activating enzyme that catalyzes the covalent conjugation of the ubiquitin-like protein product of ISG15 to additional interferon stimulated proteins (ISGs) as well as other cellular proteins such as P53 in a process termed protein ISGylation (PubMed:27545325). Plays an essential role in antiviral immunity together with ISG15 by restricting the replication of many viruses including rabies virus, influenza virus, sindbis virus, rotavirus or human cytomegalovirus (PubMed:16254333, PubMed:19073728, PubMed:29056542, PubMed:29743376, PubMed:37722521). For example, ISG15 modification of influenza A protein NS1 disrupts the association of the NS1 with importin-alpha leading to NS1 nuclear import inhibition (PubMed:20133869). ISGylation of human cytomegalovirs protein UL26 regulates its stability and inhibits its activities to suppress NF-kappa-B signaling (PubMed:27564865).<ref>PMID:16254333</ref> <ref>PMID:19073728</ref> <ref>PMID:20133869</ref> <ref>PMID:27545325</ref> <ref>PMID:27564865</ref> <ref>PMID:29056542</ref> <ref>PMID:29743376</ref> <ref>PMID:37722521</ref>
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== Publication Abstract from PubMed ==
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The attachment of the ubiquitin-like protein ISG15 to substrates by specific E1-E2-E3 enzymes is a well-established signalling mechanism of the innate immune response. Here, we present a 3.45 A cryo-EM structure of a chemically trapped UBE1L-UBE2L6 complex bound to activated ISG15. This structure reveals the details of the first steps of ISG15 recognition and UBE2L6 recruitment by UBE1L (also known as UBA7). Taking advantage of viral effector proteins from severe acute respiratory coronavirus 2 (SARS-CoV-2) and influenza B virus (IBV), we validate the structure and confirm the importance of the ISG15 C-terminal ubiquitin-like domain in the adenylation reaction. Moreover, biochemical characterization of the UBE1L-ISG15 and UBE1L-UBE2L6 interactions enables the design of ISG15 and UBE2L6 mutants with altered selectively for the ISG15 and ubiquitin conjugation pathways. Together, our study helps to define the molecular basis of these interactions and the specificity determinants that ensure the fidelity of ISG15 signalling during the antiviral response.
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Insights into the ISG15 transfer cascade by the UBE1L activating enzyme.,Wallace I, Baek K, Prabu JR, Vollrath R, von Gronau S, Schulman BA, Swatek KN Nat Commun. 2023 Dec 2;14(1):7970. doi: 10.1038/s41467-023-43711-3. PMID:38042859<ref>PMID:38042859</ref>
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==See Also==
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*[[3D structures of Ubiquitin activating enzyme|3D structures of Ubiquitin activating enzyme]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
== References ==
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Current revision

Structure of the UBE1L activating enzyme bound to ISG15 and UBE2L6

PDB ID 8oif

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