5zck

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== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/RIPK3_HUMAN RIPK3_HUMAN]] Essential for necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members. Upon induction of necrosis, RIPK3 interacts with, and phosphorylates RIPK1 and MLKL 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.<ref>PMID:19498109</ref> <ref>PMID:19524512</ref> <ref>PMID:19524513</ref> <ref>PMID:22265413</ref> <ref>PMID:22265414</ref> <ref>PMID:22421439</ref>
[[http://www.uniprot.org/uniprot/RIPK3_HUMAN RIPK3_HUMAN]] Essential for necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members. Upon induction of necrosis, RIPK3 interacts with, and phosphorylates RIPK1 and MLKL 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.<ref>PMID:19498109</ref> <ref>PMID:19524512</ref> <ref>PMID:19524513</ref> <ref>PMID:22265413</ref> <ref>PMID:22265414</ref> <ref>PMID:22421439</ref>
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== Publication Abstract from PubMed ==
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The RIPK1-RIPK3 necrosome is an amyloid signaling complex that initiates TNF-induced necroptosis, serving in human immune defense, cancer, and neurodegenerative diseases. RIPK1 and RIPK3 associate through their RIP homotypic interaction motifs with consensus sequences IQIG (RIPK1) and VQVG (RIPK3). Using solid-state nuclear magnetic resonance, we determined the high-resolution structure of the RIPK1-RIPK3 core. RIPK1 and RIPK3 alternately stack (RIPK1, RIPK3, RIPK1, RIPK3, etc.) to form heterotypic beta sheets. Two such beta sheets bind together along a compact hydrophobic interface featuring an unusual ladder of alternating Ser (from RIPK1) and Cys (from RIPK3). The crystal structure of a four-residue RIPK3 consensus sequence is consistent with the architecture determined by NMR. The RIPK1-RIPK3 core is the first detailed structure of a hetero-amyloid and provides a potential explanation for the specificity of hetero- over homo-amyloid formation and a structural basis for understanding the mechanisms of signal transduction.
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The Structure of the Necrosome RIPK1-RIPK3 Core, a Human Hetero-Amyloid Signaling Complex.,Mompean M, Li W, Li J, Laage S, Siemer AB, Bozkurt G, Wu H, McDermott AE Cell. 2018 May 17;173(5):1244-1253.e10. doi: 10.1016/j.cell.2018.03.032. Epub, 2018 Apr 19. PMID:29681455<ref>PMID:29681455</ref>
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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 ==
== References ==
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<references/>

Revision as of 07:43, 23 May 2018

Structure of the RIP3 core region

5zck, resolution 1.27Å

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