Genomic clustering and homology between HET-S and the NWD2 STAND protein in various fungal genomes

• Published in: PloS one 2012-04, Vol.7 (4), p.e34854-e34854
• Main Authors: Daskalov, Asen, Paoletti, Mathieu, Ness, Frédérique, Saupe, Sven J
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Amino acids; Amyloid - chemistry; Amyloid - genetics; Amyloid - metabolism; Analysis; Apoptosis; ATPases; Biology; Biosynthesis; Cell death; Cellular Biology; Clustering; Conservation; Conserved Sequence; Evolutionary conservation; Fungal Proteins - chemistry; Fungal Proteins - genetics; Fungi; Genes; Genome, Fungal; Genomes; Genomic analysis; Genomics; Homology; Infectious diseases; Life Sciences; Medicine; Models, Molecular; Molecular Sequence Data; Multigene Family; N-Terminus; Nectria - genetics; Nectria - metabolism; Podospora - genetics; Podospora - metabolism; Polymers; Prion protein; Prions; Prions - chemistry; Prions - genetics; Prions - metabolism; Propagation; Protein folding; Protein Isoforms - chemistry; Protein Isoforms - genetics; Protein Multimerization; Protein Structure, Tertiary; Proteins; Sequence Homology, Amino Acid; Signal Transduction; Toxicity; Transduction; Trends
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0034854

Prions are infectious proteins propagating as self-perpetuating amyloid polymers. The [Het-s] prion of Podospora anserina is involved in a cell death process associated with non-self recognition. The prion forming domain (PFD) of HET-s adopts a β-solenoid amyloid structure characterized by the two fold repetition of an elementary triangular motif. [Het-s] induces cell death when interacting with HET-S, an allelic variant of HET-s. When templated by [Het-s], HET-S undergoes a trans-conformation, relocates to the cell membrane and induces toxicity. Here, comparing HET-s homologs from different species, we devise a consensus for the HET-s elementary triangular motif. We use this motif to screen genomic databases and find a match to the N-terminus of NWD2, a STAND protein, encoded by the gene immediately adjacent to het-S. STAND proteins are signal transducing ATPases which undergo ligand-induced oligomerisation. Homology modelling predicts that the NWD2 N-terminal region adopts a HET-s-like fold. We propose that upon NWD2 oligomerisation, these N-terminal extensions adopt the β-solenoid fold and template HET-S to adopt the amyloid fold and trigger toxicity. We extend this model to a putative prion, the σ infectious element in Nectria haematococca, because the s locus controlling propagation of σ also encodes a STAND protein and displays analogous features. Comparative genomic analyses indicate evolutionary conservation of these STAND/prion-like gene pairs, identify a number of novel prion candidates and define, in addition to the HET-s PFD motif, two distinct, novel putative PFD-like motifs. We suggest the existence, in the fungal kingdom, of a widespread and evolutionarily conserved mode of signal transduction based on the transmission of an amyloid-fold from a NOD-like STAND receptor protein to an effector protein.