View the Current Issue

Article

  • The EMBO Journal (2003) 22, 2071 - 2081
  • doi:10.1093/emboj/cdg213

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

Axelle Balguerie1,7, Suzana Dos Reis1,7, Christiane Ritter2, Stéphane Chaignepain3, Bénédicte Coulary-Salin4, Vincent Forge5, Katell Bathany3, Ioan Lascu6, Jean-Marie Schmitter3, Roland Riek2 and Sven J. Saupe1

  1. Laboratoire de Génétique Moléculaire des Champignons, Institut de Biochimie et de Génétique Cellulaires, UMR 5095 CNRS/Université de Bordeaux 2, 1 rue Camille St Saëns, 33077 Bordeaux cedex, France
  2. Structural Biology Laboratory, The Salk Institute for Biological Studies, PO Box 85800, San Diego, CA 92186-5800, USA
  3. Institut Européen de Chimie et Biologie, CNRS FRE 2247, 16 Av. Pey Berland, 33607 Pessac cedex, France
  4. Service de Microscopie, Institut de Biochimie et de Génétique Cellulaires, UMR 5095 CNRS/Université de Bordeaux 2, 1 rue Camille St Saëns, 33077 Bordeaux cedex, France
  5. Laboratoire de Biophysique Moléculaire et Cellulaire, UMR 5090, Département de Biologie Moléculaire et Structurale, CEA-Grenoble, 17 rue de Martyrs, 38054 Grenoble cedex 9, France
  6. Laboratoire d'Enzymologie Moléculaire, Institut de Biochimie et de Génétique Cellulaires, UMR 5095 CNRS/Université de Bordeaux 2, 1 rue Camille St Saëns, 33077 Bordeaux cedex, France
  7. A.Balguerie and S.Dos Reis contributed equally to this work

Correspondence to:

Sven J. Saupe, E-mail: sven.saupe@ibgc.u-bordeaux2.fr

Received 3 February 2003; Accepted 11 March 2003; Revised 10 March 2003

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.

  • Keywords:

    • amyloid,
    • filamentous fungi,
    • heterokaryon incompatibility,
    • prion