Structural basis for amyloid fibril assembly by the master cell-signaling regulator receptor-interacting protein kinase 1.

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 hydroph

SUBMITTER: Polonio P 

PROVIDER: S-EPMC12575786 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature