9HR6
cryoEM structure of amyloid fibrils formed by human RIPK1
Summary for 9HR6
| Entry DOI | 10.2210/pdb9hr6/pdb |
| Related | 9HR9 |
| EMDB information | 52356 |
| Descriptor | Receptor-interacting serine/threonine-protein kinase 1 (1 entity in total) |
| Functional Keywords | amyloid, kinase, protein fibril |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 5 |
| Total formula weight | 48283.02 |
| Authors | Lopez-Alonso, J.P.,Ubarretxena-Belandia, I.,Jiang, H. (deposition date: 2024-12-17, release date: 2025-09-17, Last modification date: 2026-04-01) |
| Primary citation | Polonio, P.,Lopez-Alonso, J.P.,Jiang, H.,Andres-Campos, S.,Escobedo-Gonzalez, F.C.,Titaux-Delgado, G.A.,Ubarretxena-Belandia, I.,Mompean, M. Structural basis for amyloid fibril assembly by the master cell-signaling regulator receptor-interacting protein kinase 1. Nat Commun, 16:9607-9607, 2025 Cited by PubMed Abstract: Amyloid fibrils can form biologically relevant functional assemblies. The RIP homotypic interaction motifs (RHIMs) in receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3) orchestrate the formation of amyloid-like fibrils essential for propagating cell death signals. While the structures of human RIPK3 (hRIPK3) homomeric fibrils and RIPK1-RIPK3 heteromeric fibrils have been elucidated, the atomic structure of human RIPK1 (hRIPK1) homomeric fibrils has remained elusive. We present a high-resolution structure of hRIPK1 RHIM-mediated amyloid fibrils, determined using an integrative approach combining cryoprobe-detected solid-state nuclear magnetic resonance spectroscopy and cryo-electron microscopy. The fibrils adopt an N-shaped fold consisting of three β-sheets stabilized by hydrophobic interactions and hydrogen bonding. A key hydrogen bond between N545 and G542 closes the β2-β3 loop, resulting in denser side-chain packing compared to hRIPK3 homomeric fibrils. These findings provide structural insights into how hRIPK1 homomeric fibrils nucleate hRIPK3 recruitment and fibrillization during necroptosis, offering broader perspectives on the molecular principles governing RHIM-mediated amyloid assembly and functional amyloids. PubMed: 41168207DOI: 10.1038/s41467-025-64621-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.57 Å) |
Structure validation
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