title: Theme and variations: evolutionary diversification of the HET-s functional amyloid motif.
abstract: In mammals and fungi, Nod-like receptors (NLR) activate downstream cell death execution proteins by a prion-like mechanism. In Podospora anserina, the NWD2 NLR activates the HET-S Helo-domain pore-forming protein by converting its prion-forming domain into a characteristic β-solenoid amyloid fold. The amyloid forming region of HET-S/s comprises two repetitions of a 21 amino acid motif. Herein, we systematically analyze the sequences of C-terminal regions of fungal HeLo and HeLo-like domain proteins to identify HET-s-related amyloid motifs (HRAM). We now identify four novel HRAM subfamilies in addition to the canonical HET-S/s subfamily. These novel motifs share the pseudo-repeat structure of HET-S/s and a specific pattern of distribution of hydrophobic and polar residues. Sequence co-variance analyses predict parallel in-register β-stacking of the two repeats and residue-residue interactions compatible with the β-solenoid fold. As described for HET-S, most genes encoding the HeLo proteins are adjacent to genes encoding NLRs also displaying HRAMs. The motifs of the NLRs are similar to those of their cognate HeLo-domain protein, indicating concerted evolution between repeats. This study shows that HET-s-related amyloid motifs are more common than anticipated and that they have diversified into discrete subfamilies that apparently share a common overall fold.
authors.affiliation: Non-self recognition in fungi, Institut de Biochimie et de Génétique Cellulaire, UMR 5095, CNRS - Université de Bordeaux, 1 rue Camille Saint Saens, 33077 Bordeaux cedex, France.
authors.forename: Asen
authors.initials: A
authors.lastname: Daskalov
authors.affiliation: 1] Team MAGNOME, INRIA - Université Bordeaux - CNRS, 33405 Talence, France [2] Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Technology, 50-370 Wroclaw, Poland.
authors.forename: Witold
authors.initials: W
authors.lastname: Dyrka
authors.affiliation: Non-self recognition in fungi, Institut de Biochimie et de Génétique Cellulaire, UMR 5095, CNRS - Université de Bordeaux, 1 rue Camille Saint Saens, 33077 Bordeaux cedex, France.
authors.forename: Sven J
authors.initials: SJ
authors.lastname: Saupe
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000235:genetics; D016000:Cluster Analysis; D016384:Consensus Sequence; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry; D056510:Position-Specific Scoring Matrices; D054730:Protein Interaction Domains and Motifs / Q000235:genetics
chemical_list: D000682:Amyloid; D005656:Fungal Proteins