6flm

From Proteopedia

(Difference between revisions)

Revision as of 07:29, 23 May 2018

Crystal structure of the human TRIM25 PRYSPRY domain

Structural highlights

6flm is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
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/6flm"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6flm is ON HOLD
+==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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FLM FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6flm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6flm OCA], [http://pdbe.org/6flm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6flm RCSB], [http://www.ebi.ac.uk/pdbsum/6flm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6flm 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:
+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:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6flm" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Cusack, S]]
+[[Category: Kowalinski, E]]
+[[Category: E3 ligase]]
+[[Category: Protein binding]]
+[[Category: Pryspry domain]]
+[[Category: Trim protein]]

6flm

From Proteopedia

Revision as of 07:29, 23 May 2018

Crystal structure of the human TRIM25 PRYSPRY domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox