RT Journal Article
SR Electronic
T1 The RHIM within the M45 protein from murine cytomegalovirus forms heteromeric amyloid fibrils with RIPK1 and RIPK3
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 324590
DO 10.1101/324590
A1 Pham, Chi L. L.
A1 Strange, Merryn
A1 O’ Carroll, Ailis
A1 Shanmugam, Nirukshan
A1 Sierecki, Emma
A1 Gambin, Yann
A1 Steain, Megan
A1 Sunde, Margaret
YR 2018
UL http://biorxiv.org/content/early/2018/06/01/324590.abstract
AB The M45 protein from murine cytomegalovirus protects infected murine cells from death by necroptosis and can protect human cells from necroptosis induced by TNFR activation, when heterologously expressed. 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 human RIPK1 and RIPK3 kinases to form heteromeric amyloid fibrils in vitro. An intact RHIM core tetrad is required for the inhibition of cell death by M45 and we show that mutation of those key tetrad residues abolishes homo- and hetero-amyloid assembly by M45 in vitro, suggesting that the amyloidogenic nature of the M45 RHIM underlies its biological activity. Our results indicate that M45 mimics the interactions made by RIPK1 with RIPK3 in forming heteromeric amyloid structures.