Domain organization and structure-function relationship of the HET-s prion protein of Podospora anserina

• Published in: The EMBO journal Vol. 22; no. 9; pp. 2071 - 2081
• Main Authors: Saupe, Sven J, Balguerie, Axelle, Reis, Suzana Dos, Ritter, Christiane, Chaignepain, Stéphane, Coulary-Salin, Bénédicte, Forge, Vincent, Bathany, Katell, Lascu, Ioan, Schmitter, Jean-Marie, Riek, Roland
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.05.2003; Blackwell Publishing Ltd; Oxford University Press
• Subjects: Amino Acid Sequence; Amino acids; amyloid; Circular Dichroism; Fibers; filamentous fungi; Fungal Proteins - chemistry; Fungal Proteins - physiology; heterokaryon incompatibility; Hydrolysis; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; prion; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Sequence Homology, Amino Acid; Sordariales - metabolism; Spectroscopy, Fourier Transform Infrared; Structure-Activity Relationship
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/cdg213

The [Het‐s] infectious element of the fungus Podospora anserina is a prion protein involved in a genetically controlled cell death reaction termed heterokaryon incompatibility. Previous analyses indicate that [Het‐s] propagates as a self‐perpetuating amyloid aggregate. The HET‐s protein is 289 amino acids in length. Herein, we identify the region of the HET‐s protein that is responsible for amyloid formation and prion propagation. The region of HET‐s spanning residues 218–289 forms amyloid fibers in vitro and allows prion propagation in vivo. Conversely, a C‐terminal deletion in HET‐s prevents amyloid aggregation in vitro and prion propagation in vivo, and abolishes the incompatibility function. In the soluble form of HET‐s, the region from residue 1 to 227 forms a well‐folded domain while the C‐terminal region is highly flexible. Together, our data establish a domain structure–function relationship for HET‐s amyloid formation, prion propagation and incompatibility activity.