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

From Proteopedia

==Structural basis for amyloid fibril assembly by the master cell-signaling regulator receptor-interacting protein kinase 1^[1] or to the article describing Jmol ^[2] to the rescue.

Function

RIPK1 (Receptor-Interacting Protein Kinase 1) is a protein that plays a central role in cell death and survival pathways, regulating inflammation and maintaining homeostasis. When polyubiquitinated, RIPK1 promotes cell proliferation and differentiation. Here, it acts as part of the TNFR signalling pathway to activate the NF-κB transcription factors. Conversely, in the absence of polyubiquitination, it can form a complex with FADD and caspase 8 to trigger apoptosis. In the case of caspase activity blockage, the assembly of RIPK1/RIPK3 fibrils can trigger necroptosis. The signalling pathway starts with the self-association of RIPK1, leading to the assembly of heteromeric RIPK1-RIPK3 fibrils (canonical necrosome), finally resulting in MLKL oligomerisation to trigger necroptosis.

Disease

RIPK1 has been reported to be involved in many neurodegenerative diseases such as AD, ALS and MS. In Alzheimer's disease, it has been shown to regulate microglial function by modulating cell inflammation.^[3]