View source for 6ggs


==Structure of RIP2 CARD filament==
<SX load='6ggs' size='340' side='right' viewer='molstar' caption='[[6ggs]], [[Resolution|resolution]] 3.94&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ggs]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GGS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6GGS FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ggs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ggs OCA], [http://pdbe.org/6ggs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ggs RCSB], [http://www.ebi.ac.uk/pdbsum/6ggs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ggs ProSAT]</span></td></tr>
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== Function ==
[[http://www.uniprot.org/uniprot/RIPK2_HUMAN RIPK2_HUMAN]] Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation.<ref>PMID:14638696</ref> <ref>PMID:17054981</ref> <ref>PMID:18079694</ref> <ref>PMID:21123652</ref>  
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== Publication Abstract from PubMed ==
Activation of the innate immune pattern recognition receptor NOD2 by the bacterial muramyl-dipeptide peptidoglycan fragment triggers recruitment of the downstream adaptor kinase RIP2, eventually leading to NF-kappaB activation and proinflammatory cytokine production. Here we show that full-length RIP2 can form long filaments mediated by its caspase recruitment domain (CARD), in common with other innate immune adaptor proteins. We further show that the NOD2 tandem CARDs bind to one end of the RIP2 CARD filament, suggesting a mechanism for polar filament nucleation by activated NOD2. We combine X-ray crystallography, solid-state NMR and high-resolution cryo-electron microscopy to determine the atomic structure of the helical RIP2 CARD filament, which reveals the intermolecular interactions that stabilize the assembly. Using structure-guided mutagenesis, we demonstrate the importance of RIP2 polymerization for the activation of NF-kappaB signalling by NOD2. Our results could be of use to develop new pharmacological strategies to treat inflammatory diseases characterised by aberrant NOD2 signalling.

RIP2 filament formation is required for NOD2 dependent NF-kappaB signalling.,Pellegrini E, Desfosses A, Wallmann A, Schulze WM, Rehbein K, Mas P, Signor L, Gaudon S, Zenkeviciute G, Hons M, Malet H, Gutsche I, Sachse C, Schoehn G, Oschkinat H, Cusack S Nat Commun. 2018 Oct 2;9(1):4043. doi: 10.1038/s41467-018-06451-3. PMID:30279485<ref>PMID:30279485</ref>

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

==See Also==
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
<references/>
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</SX>
[[Category: Large Structures]]
[[Category: Cusack, S]]
[[Category: Desfosses, A]]
[[Category: Gutsche, I]]
[[Category: Hons, M]]
[[Category: Malet, H]]
[[Category: Pellegrini, E]]
[[Category: Sachse, C]]
[[Category: Schoehn, G]]
[[Category: Card]]
[[Category: Filament]]
[[Category: Helical]]
[[Category: Rip2]]
[[Category: Transferase]]