View source for 6flm


==Crystal structure of the human TRIM25 PRYSPRY domain==
<StructureSection load='6flm' size='340' side='right'caption='[[6flm]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6flm]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FLM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FLM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.009&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6flm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6flm OCA], [https://pdbe.org/6flm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6flm RCSB], [https://www.ebi.ac.uk/pdbsum/6flm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6flm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TRI25_HUMAN TRI25_HUMAN] Functions as a ubiquitin E3 ligase and as an ISG15 E3 ligase. Involved in innate immune defense against viruses by mediating ubiquitination of DDX58. Mediates 'Lys-63'-linked polyubiquitination of the DDX58 N-terminal CARD-like region which is crucial for triggering the cytosolic signal transduction that leads to the production of interferons in response to viral infection. Promotes ISGylation of 14-3-3 sigma (SFN), an adapter protein implicated in the regulation of a large spectrum signaling pathway. Mediates estrogen action in various target organs.<ref>PMID:16352599</ref> <ref>PMID:17069755</ref> <ref>PMID:17392790</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
RIG-I is a viral RNA sensor that induces the production of type I interferon (IFN) in response to infection with a variety of viruses. Modification of RIG-I with K63-linked poly-ubiquitin chains, synthesised by TRIM25, is crucial for activation of the RIG-I/MAVS signalling pathway. TRIM25 activity is targeted by influenza A virus non-structural protein 1 (NS1) to suppress IFN production and prevent an efficient host immune response. Here we present structures of the human TRIM25 coiled-coil-PRYSPRY module and of complexes between the TRIM25 coiled-coil domain and NS1. These structures show that binding of NS1 interferes with the correct positioning of the PRYSPRY domain of TRIM25 required for substrate ubiquitination and provide a mechanistic explanation for how NS1 suppresses RIG-I ubiquitination and hence downstream signalling. In contrast, the formation of unanchored K63-linked poly-ubiquitin chains is unchanged by NS1 binding, indicating that RING dimerisation of TRIM25 is not affected by NS1.

Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition.,Koliopoulos MG, Lethier M, van der Veen AG, Haubrich K, Hennig J, Kowalinski E, Stevens RV, Martin SR, Reis E Sousa C, Cusack S, Rittinger K Nat Commun. 2018 May 8;9(1):1820. doi: 10.1038/s41467-018-04214-8. PMID:29739942<ref>PMID:29739942</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6flm" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cusack S]]
[[Category: Kowalinski E]]