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==Crystal structure of human ISG15 in complex with NS1 N-terminal region from influenza B virus, Northeast Structural Genomics Consortium Target IDs HX6481, HR2873, and OR2==
==Crystal structure of human ISG15 in complex with NS1 N-terminal region from influenza B virus, Northeast Structural Genomics Consortium Target IDs HX6481, HR2873, and OR2==
<StructureSection load='3sdl' size='340' side='right' caption='[[3sdl]], [[Resolution|resolution]] 2.29&Aring;' scene=''>
<StructureSection load='3sdl' size='340' side='right'caption='[[3sdl]], [[Resolution|resolution]] 2.29&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3sdl]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Influenza_b_virus Influenza b virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SDL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SDL FirstGlance]. <br>
<table><tr><td colspan='2'>[[3sdl]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_B_virus_(B/Lee/1940) Influenza B virus (B/Lee/1940)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SDL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SDL FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1z2m|1z2m]]</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.29&#8491;</td></tr>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11520 Influenza B virus]), G1P2, ISG15, UCRP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3sdl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sdl OCA], [https://pdbe.org/3sdl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sdl RCSB], [https://www.ebi.ac.uk/pdbsum/3sdl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sdl ProSAT]</span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3sdl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sdl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sdl RCSB], [http://www.ebi.ac.uk/pdbsum/3sdl PDBsum]</span></td></tr>
</table>
<table>
== Function ==
<div style="background-color:#fffaf0;">
[https://www.uniprot.org/uniprot/NS1_INBLE NS1_INBLE] Binds and inhibits the ubiquitin-like protein G1P2/ISG15, which is an early antiviral protein. Inhibits IRF-3 nuclear translocation and activation. Inhibits IFN-beta promoter activation; this inhibition is not dsRNA-binding dependent Prevents EIF2AK2/PKR activation, either by binding double strand RNA or by interacting directly with EIF2AK2/PKR. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells.<ref>PMID:15479798</ref>  
== Publication Abstract from PubMed ==
Interferon-induced ISG15 conjugation plays an important antiviral role against several viruses, including influenza viruses. The NS1 protein of influenza B virus (NS1B) specifically binds only human and nonhuman primate ISG15s and inhibits their conjugation. To elucidate the structural basis for the sequence-specific recognition of human ISG15, we determined the crystal structure of the complex formed between human ISG15 and the N-terminal region of NS1B (NS1B-NTR). The NS1B-NTR homodimer interacts with two ISG15 molecules in the crystal and also in solution. The two ISG15-binding sites on the NS1B-NTR dimer are composed of residues from both chains, namely residues in the RNA-binding domain (RBD) from one chain, and residues in the linker between the RBD and the effector domain from the other chain. The primary contact region of NS1B-NTR on ISG15 is composed of residues at the junction of the N-terminal ubiquitin-like (Ubl) domain and the short linker region between the two Ubl domains, explaining why the sequence of the short linker in human and nonhuman primate ISG15s is essential for the species-specific binding of these ISG15s. In addition, the crystal structure identifies NS1B-NTR binding sites in the N-terminal Ubl domain of ISG15, and shows that there are essentially no contacts with the C-terminal Ubl domain of ISG15. Consequently, NS1B-NTR binding to ISG15 would not occlude access of the C-terminal Ubl domain of ISG15 to its conjugating enzymes. Nonetheless, transfection assays show that NS1B-NTR binding of ISG15 is responsible for the inhibition of interferon-induced ISG15 conjugation in cells.
 
Structural basis for the sequence-specific recognition of human ISG15 by the NS1 protein of influenza B virus.,Guan R, Ma LC, Leonard PG, Amer BR, Sridharan H, Zhao C, Krug RM, Montelione GT Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13468-73. Epub 2011 Aug 1. PMID:21808041<ref>PMID:21808041</ref>
 
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
</div>
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Influenza b virus]]
[[Category: Large Structures]]
[[Category: Guan, R.]]
[[Category: Guan R]]
[[Category: Krug, R M.]]
[[Category: Krug RM]]
[[Category: Ma, L C.]]
[[Category: Ma L-C]]
[[Category: Montelione, G T.]]
[[Category: Montelione GT]]
[[Category: NESG, Northeast Structural Genomics Consortium.]]
[[Category: Nesg]]
[[Category: Northeast structural genomics consortium]]
[[Category: Protein complex]]
[[Category: Psi-biology]]
[[Category: Structural genomic]]
[[Category: Viral protein-antiviral protein complex]]
[[Category: Viral protein/antiviral protein]]

Latest revision as of 12:54, 14 March 2024

Crystal structure of human ISG15 in complex with NS1 N-terminal region from influenza B virus, Northeast Structural Genomics Consortium Target IDs HX6481, HR2873, and OR2

3sdl, resolution 2.29Å

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