Structural similarity between the prion domain of HET-s and a homologue can explain amyloid cross-seeding in spite of limited sequence identity

J Mol Biol. 2010 Sep 17;402(2):311-25. doi: 10.1016/j.jmb.2010.06.053. Epub 2010 Jul 1.


We describe a distant homologue of the fungal HET-s prion, which is found in the fungus Fusarium graminearum. The domain FgHET-s(218-289), which corresponds to the prion domain in HET-s from Podospora anserina, forms amyloid fibrils in vitro and is able to efficiently cross-seed HET-s(218-289) prion formation. We structurally characterize FgHET-s(218-289), which displays 38% sequence identity with HET-s(218-289). Solid-state NMR and hydrogen/deuterium exchange detected by NMR show that the fold and a number of structural details are very similar for the prion domains of the two proteins. This structural similarity readily explains why cross-seeding occurs here in spite of the sequence divergence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid / metabolism*
  • Amyloid / ultrastructure
  • Fungal Proteins / chemistry*
  • Fungal Proteins / genetics
  • Fusarium / chemistry*
  • Fusarium / genetics
  • Macromolecular Substances
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Podospora / chemistry*
  • Podospora / genetics
  • Prions / chemistry*
  • Prions / genetics
  • Protein Folding
  • Protein Multimerization
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Sequence Homology, Amino Acid


  • Amyloid
  • Fungal Proteins
  • HET-S protein, Podospora anserina
  • Macromolecular Substances
  • Prions