Structural highlights
Publication Abstract from PubMed
The RIPK1-RIPK3 necrosome is an amyloid signaling complex that initiates TNF-induced necroptosis, serving in human immune defense, cancer, and neurodegenerative diseases. RIPK1 and RIPK3 associate through their RIP homotypic interaction motifs with consensus sequences IQIG (RIPK1) and VQVG (RIPK3). Using solid-state nuclear magnetic resonance, we determined the high-resolution structure of the RIPK1-RIPK3 core. RIPK1 and RIPK3 alternately stack (RIPK1, RIPK3, RIPK1, RIPK3, etc.) to form heterotypic beta sheets. Two such beta sheets bind together along a compact hydrophobic interface featuring an unusual ladder of alternating Ser (from RIPK1) and Cys (from RIPK3). The crystal structure of a four-residue RIPK3 consensus sequence is consistent with the architecture determined by NMR. The RIPK1-RIPK3 core is the first detailed structure of a hetero-amyloid and provides a potential explanation for the specificity of hetero- over homo-amyloid formation and a structural basis for understanding the mechanisms of signal transduction.
The Structure of the Necrosome RIPK1-RIPK3 Core, a Human Hetero-Amyloid Signaling Complex.,Mompean M, Li W, Li J, Laage S, Siemer AB, Bozkurt G, Wu H, McDermott AE Cell. 2018 May 17;173(5):1244-1253.e10. doi: 10.1016/j.cell.2018.03.032. Epub, 2018 Apr 19. PMID:29681455[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mompean M, Li W, Li J, Laage S, Siemer AB, Bozkurt G, Wu H, McDermott AE. The Structure of the Necrosome RIPK1-RIPK3 Core, a Human Hetero-Amyloid Signaling Complex. Cell. 2018 May 17;173(5):1244-1253.e10. doi: 10.1016/j.cell.2018.03.032. Epub, 2018 Apr 19. PMID:29681455 doi:http://dx.doi.org/10.1016/j.cell.2018.03.032
