NMR characterization of an assembling RHIM (RIP homotypic interaction motif) amyloid reveals a cryptic region for self-recognition.

ABSTRACT: The RIP homotypic interaction motif (RHIM) is an essential protein motif in inflammatory signaling and certain cell death pathways. RHIM signaling occurs following the assembly of functional amyloids, and while the structural biology of such higher-order RHIM complexes has started to emerge, the conformations and dynamics of nonassembled RHIMs remain unknown. Here, using solution NMR spectroscopy, we report the characterization of the monomeric form of the RHIM in receptor-interacting protein kinase 3 (RIPK3), a fundamental protein in human immunity. Our results establish that the RHIM of RIPK3 is an intrinsically disordered protein motif, contrary to prediction, and that exchange dynamics between free monomers and amyloid-bound RIPK3 monomers involve a 20-residue stretch outside the RHIM

SUBMITTER: Pham CLL 

PROVIDER: S-EPMC10070927 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature