View source for 6fln


==Crystal structure of the human TRIM25 coiled-coil and PRYSPRY domains==
<StructureSection load='6fln' size='340' side='right' caption='[[6fln]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fln]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FLN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FLN FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6flm|6flm]], [[4ltb|4ltb]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6fln FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fln OCA], [http://pdbe.org/6fln PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fln RCSB], [http://www.ebi.ac.uk/pdbsum/6fln PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fln ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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 6fln" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Cusack, S]]
[[Category: Lethier, M]]
[[Category: Coiled-coil]]
[[Category: E3 ligase]]
[[Category: Protein binding]]
[[Category: Pryspry domain]]
[[Category: Trim protein]]