title: Amyloid fibrils of the HET-s(218-289) prion form a beta solenoid with a triangular hydrophobic core.
abstract: Prion and nonprion forms of proteins are believed to differ solely in their three-dimensional structure, which is therefore of paramount importance for the prion function. However, no atomic-resolution structure of the fibrillar state that is likely infectious has been reported to date. We present a structural model based on solid-state nuclear magnetic resonance restraints for amyloid fibrils from the prion-forming domain (residues 218 to 289) of the HET-s protein from the filamentous fungus Podospora anserina. On the basis of 134 intra- and intermolecular experimental distance restraints, we find that HET-s(218-289) forms a left-handed beta solenoid, with each molecule forming two helical windings, a compact hydrophobic core, at least 23 hydrogen bonds, three salt bridges, and two asparagine ladders. The structure is likely to have broad implications for understanding the infectious amyloid state.
authors.affiliation: Physical Chemistry, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Wasmer
authors.forename: Adam
authors.initials: A
authors.lastname: Lange
authors.forename: Hélène
authors.initials: H
authors.lastname: Van Melckebeke
authors.forename: Ansgar B
authors.initials: AB
authors.lastname: Siemer
authors.forename: Roland
authors.initials: R
authors.lastname: Riek
authors.forename: Beat H
authors.initials: BH
authors.lastname: Meier
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D005656:Fungal Proteins / Q000737:chemistry*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry; D048468:Podospora / Q000737:chemistry*; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D000682:Amyloid; D005656:Fungal Proteins; C083891:HET-S protein, Podospora anserina; D010455:Peptides; D011328:Prions