Structural highlights
Function
[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).[1]
Publication Abstract from PubMed
RIPK3 amyloid complex plays crucial roles during TNF-induced necroptosis and in response to immune defense in both human and mouse. Here, we have structurally characterized mouse RIPK3 homogeneous self-assembly using solid-state NMR, revealing a well-ordered N-shaped amyloid core structure featured with 3 parallel in-register beta-sheets. This structure differs from previously published human RIPK1/RIPK3 hetero-amyloid complex structure, which adopted a serpentine fold. Functional studies indicate both RIPK1-RIPK3 binding and RIPK3 amyloid formation are essential but not sufficient for TNF-induced necroptosis. The structural integrity of RIPK3 fibril with three beta-strands is necessary for signaling. Molecular dynamics simulations with a mouse RIPK1/RIPK3 model indicate that the hetero-amyloid is less stable when adopting the RIPK3 fibril conformation, suggesting a structural transformation of RIPK3 from RIPK1-RIPK3 binding to RIPK3 amyloid formation. This structural transformation would provide the missing link connecting RIPK1-RIPK3 binding to RIPK3 homo-oligomer formation in the signal transduction.
The amyloid structure of mouse RIPK3 (receptor interacting protein kinase 3) in cell necroptosis.,Wu XL, Hu H, Dong XQ, Zhang J, Wang J, Schwieters CD, Liu J, Wu GX, Li B, Lin JY, Wang HY, Lu JX Nat Commun. 2021 Mar 12;12(1):1627. doi: 10.1038/s41467-021-21881-2. PMID:33712586[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rebsamen M, Heinz LX, Meylan E, Michallet MC, Schroder K, Hofmann K, Vazquez J, Benedict CA, Tschopp J. DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB. EMBO Rep. 2009 Aug;10(8):916-22. doi: 10.1038/embor.2009.109. Epub 2009 Jul 10. PMID:19590578 doi:http://dx.doi.org/10.1038/embor.2009.109
- ↑ Wu XL, Hu H, Dong XQ, Zhang J, Wang J, Schwieters CD, Liu J, Wu GX, Li B, Lin JY, Wang HY, Lu JX. The amyloid structure of mouse RIPK3 (receptor interacting protein kinase 3) in cell necroptosis. Nat Commun. 2021 Mar 12;12(1):1627. doi: 10.1038/s41467-021-21881-2. PMID:33712586 doi:http://dx.doi.org/10.1038/s41467-021-21881-2
