Viral M45 and necroptosis-associated proteins form heteromeric amyloid assemblies

ABSTRACT: The murine cytomegalovirus protein M45 protects infected mouse cells from necroptotic death, and when heterologously expressed, can protect human cells from necroptosis induced by tumour necrosis factor receptor (TNFR) activation. Here, we show that the N terminal 90 residues of the M45 protein, which contain a RIP Homotypic Interaction Motif (RHIM), are sufficient to confer protection against TNFR-induced necroptosis. This N-terminal region of M45 drives rapid self-assembly into homo-oligomeric amyloid fibrils, and interacts with the RHIMs of the human kinases RIPK1 and RIPK3, and the Z-DNA binding protein 1 (ZBP1), to form heteromeric amyloid fibrils in vitro. Mutation of the tetrad residues in the M45 RHIM attenuates homo- and hetero-amyloid assembly by M45, suggesting that the amyloido

SUBMITTER: Dr. Chi, L.L. Pham 

PROVIDER: S-SCDT-EMBOR-2018-46518V1 | biostudies-other |

REPOSITORIES: biostudies-other