6fln

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the human TRIM25 coiled-coil and PRYSPRY domains

Structural highlights

6fln is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	6flm, 4ltb
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zou W, Zhang DE. The interferon-inducible ubiquitin-protein isopeptide ligase (E3) EFP also functions as an ISG15 E3 ligase. J Biol Chem. 2006 Feb 17;281(7):3989-94. Epub 2005 Dec 13. PMID:16352599 doi:http://dx.doi.org/10.1074/jbc.M510787200
↑ Nakasato N, Ikeda K, Urano T, Horie-Inoue K, Takeda S, Inoue S. A ubiquitin E3 ligase Efp is up-regulated by interferons and conjugated with ISG15. Biochem Biophys Res Commun. 2006 Dec 15;351(2):540-6. Epub 2006 Oct 18. PMID:17069755 doi:http://dx.doi.org/10.1016/j.bbrc.2006.10.061
↑ Gack MU, Shin YC, Joo CH, Urano T, Liang C, Sun L, Takeuchi O, Akira S, Chen Z, Inoue S, Jung JU. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature. 2007 Apr 19;446(7138):916-920. PMID:17392790 doi:http://dx.doi.org/10.1038/nature05732
↑ 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. Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition. Nat Commun. 2018 May 8;9(1):1820. doi: 10.1038/s41467-018-04214-8. PMID:29739942 doi:http://dx.doi.org/10.1038/s41467-018-04214-8

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6fln"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6fln is ON HOLD
+==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.
-Authors: Cusack, S., Lethier, M.
+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>
-Description: Crystal structure of the human TRIM25 coiled-coil and PRYSPRY domains
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Lethier, M]]
+<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]]

6fln

From Proteopedia

Current revision

Crystal structure of the human TRIM25 coiled-coil and PRYSPRY domains

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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