%0 Journal Article %A Xia-lian Wu %A Hong Hu %A Xing-qi Dong %A Jing Zhang %A Jian Wang %A Charles D. Schwieters %A Jing Liu %A Guo-xiang Wu %A Bing Li %A Jing-yu Lin %A Hua-yi Wang %A Jun-xia Lu %T The Amyloid Structure of Mouse RIPK3 (Receptor Interacting Protein Kinase 3) in Cell Necroptosis %D 2020 %R 10.1101/2020.07.10.196980 %J bioRxiv %P 2020.07.10.196980 %X RIPK3 amyloid complex plays crucial roles in execution of TNF-induced necroptosis and in response to immune defense in both human and mouse. We have structurally characterized the mouse RIPK3 homogeneous self-assembly using solid-state NMR, illustrating a well-ordered N-shaped amyloid core structure featured with 3 parallel in-register β-sheets. The structure is different from previously published human RIPK1/RIPK3 hetero-amyloid complex. Functional studies indicate both RIPK1-RIPK3 binding and RIPK3 amyloid formation are essential but not sufficient for RIPK3-mediated necroptosis. The structural integrity of RIPK3 fibril with three β-strands is necessary for the signaling. Molecular dynamics simulation of the mouse RIPK1/RIPK3 model indicates less stable for the hetero-amyloid to adopt RIPK3 fibril conformation, suggesting a structural transformation of RIPK3 from RIPK1-RIPK3 binding to RIPK3 amyloid formation. This structural transformation is revealed for the first time, providing a missing link connecting RIPK1-RIPK3 binding to RIPK3 homo-oligomer formation in the signal transduction.Competing Interest StatementThe authors have declared no competing interest. %U https://www.biorxiv.org/content/biorxiv/early/2020/07/11/2020.07.10.196980.full.pdf