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

EMBO J. 2003 May 1;22(9):2071-81. doi: 10.1093/emboj/cdg213.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Circular Dichroism
  • Fungal Proteins / chemistry*
  • Fungal Proteins / physiology*
  • Hydrolysis
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Sordariales / metabolism*
  • Spectroscopy, Fourier Transform Infrared
  • Structure-Activity Relationship

Substances

  • Fungal Proteins
  • HET-S protein, Podospora anserina
  • Recombinant Proteins