4m66

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{{STRUCTURE_4m66| PDB=4m66 | SCENE= }}
 
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===Crystal structure of the mouse RIP3 kinase domain===
 
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==Function==
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==Crystal structure of the mouse RIP3 kinase domain==
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[[http://www.uniprot.org/uniprot/RIPK3_MOUSE RIPK3_MOUSE]] Essential for programmed necrosis in response to death-inducing TNF-alpha family members. Upon induction of necrosis, RIPK3 interacts with, and phosphorylates RIPK1 to form a necrosis-inducing complex. RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL. These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production (By similarity).<ref>PMID:19590578</ref>
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<StructureSection load='4m66' size='340' side='right'caption='[[4m66]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4m66]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M66 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M66 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.401&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4m66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m66 OCA], [https://pdbe.org/4m66 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m66 RCSB], [https://www.ebi.ac.uk/pdbsum/4m66 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m66 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/RIPK3_MOUSE RIPK3_MOUSE] Essential for programmed necrosis in response to death-inducing TNF-alpha family members. Upon induction of necrosis, RIPK3 interacts with, and phosphorylates RIPK1 to form a necrosis-inducing complex. RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL. These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production (By similarity).<ref>PMID:19590578</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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RIP3 is an essential upstream kinase in necroptosis. The pseudokinase MLKL functions as a substrate of RIP3 to mediate downstream signaling. The molecular mechanism by which RIP3 recognizes and phosphorylates MLKL remains unknown. Here, we report the crystal structures of the mouse RIP3 kinase domain, the MLKL kinase-like domain, and a binary complex between the two. Both RIP3 and MLKL adopt the canonical kinase fold. Free RIP3 exists in an active conformation, whereas MLKL-bound RIP3 is stabilized by AMP-PNP to adopt an inactive conformation. The formation of the RIP3-MLKL complex, involving their respective N- and C-lobes, is accompanied by pronounced conformational changes of the alphaC helix and activation loop in RIP3 and the corresponding structural elements in MLKL. RIP3-mediated MLKL phosphorylation, though important for downstream signaling, is dispensable for stable complex formation between RIP3 and MLKL. Our study serves as a framework for mechanistic understanding of RIP3-mediated necroptotic signaling.
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==About this Structure==
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Structural Insights into RIP3-Mediated Necroptotic Signaling.,Xie T, Peng W, Yan C, Wu J, Gong X, Shi Y Cell Rep. 2013 Oct 17;5(1):70-8. doi: 10.1016/j.celrep.2013.08.044. Epub 2013 Oct, 3. PMID:24095729<ref>PMID:24095729</ref>
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[[4m66]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M66 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<references group="xtra"/><references/>
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</div>
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<div class="pdbe-citations 4m66" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Peng W]]
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[[Category: Peng, W.]]
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[[Category: Shi Y]]
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[[Category: Shi, Y.]]
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[[Category: Wu J]]
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[[Category: Wu, J.]]
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[[Category: Xie T]]
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[[Category: Xie, T.]]
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[[Category: Yan C]]
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[[Category: Yan, C.]]
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[[Category: Kinase]]
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[[Category: Protein phosphorylation]]
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[[Category: Transferase]]
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Current revision

Crystal structure of the mouse RIP3 kinase domain

PDB ID 4m66

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