Structural similarity between the prion domain of HET-s and a homologue can explain amyloid cross-seeding in spite of limited sequence identity.
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.
Wasmer
Christian
C
Physical Chemistry, ETH Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
Zimmer
Agnes
A
Sabaté
Raimon
R
Soragni
Alice
A
Saupe
Sven J
SJ
Ritter
Christiane
C
Meier
Beat H
BH
D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism* / Q000648:ultrastructure; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics; D005670:Fusarium / Q000737:chemistry* / Q000235:genetics; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D048468:Podospora / Q000737:chemistry* / Q000235:genetics; D011328:Prions / Q000737:chemistry* / Q000235:genetics; D017510:Protein Folding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D000682:Amyloid; D005656:Fungal Proteins; C083891:HET-S protein, Podospora anserina; D046911:Macromolecular Substances; D011328:Prions