title: Evolutionary link between metazoan RHIM motif and prion-forming domain of fungal heterokaryon incompatibility factor HET-s/HET-s.
abstract: The Rip homotypic interaction motif (RHIM) is a short, non-globular sequence stretch that mediates a key interaction of mammalian necroptosis signaling. In order to understand its unusual oligomerization properties, we set out to trace the evolutionary origins of the RHIM motif by identifying distantly related protein motifs that might employ the same binding mode. The RHIM motif was found to be related to the prion-forming domain of the HET-s protein, which oligomerizes by forming structurally well-characterized fibrils and is involved in fungal heterokaryon incompatibility. This evolutionary relationship explains the recently reported propensity of mammalian RHIM motifs to form amyloid fibrils, but suggests that these fibrils have a different structural architecture than currently assumed. These findings, together with numerous observations of RHIM-like motifs in immunity proteins from a wide range of species, provide insight to the modern innate immunity pathways in animals, plants and fungi.
authors.affiliation: 1] Centre de Recherches de Biochimie Macromoléculaire, CNRS- UMR 5237, 1919 Route de Mende, 34293 Montpellier, Cedex 5, France [2] Institut de Biologie Computationnelle, 860 rue St Priest, 34095 Montpellier Cedex 5, France [3] University ITMO, 49 Kronverksky, av. 197101 St Petersburg, Russia.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kajava
authors.affiliation: Institute for Genetics, University of Cologne, Zülpicher Strasse 47a, D- 50674 Cologne, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Klopffleisch
authors.affiliation: Institute for Genetics, University of Cologne, Zülpicher Strasse 47a, D- 50674 Cologne, Germany.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Chen
authors.affiliation: Institute for Genetics, University of Cologne, Zülpicher Strasse 47a, D- 50674 Cologne, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Hofmann
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011328:Prions / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
chemical_list: D005656:Fungal Proteins; D019476:Insect Proteins; D011328:Prions