Amyloid Fibrils of the HET-s(218–289) Prion Form a β Solenoid with a Triangular Hydrophobic Core
Christian Wasmer,*
Adam Lange,*
Hélène Van Melckebeke,*
Ansgar B. Siemer,
Roland Riek,
Beat H. Meier
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 β 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.
Physical Chemistry, ETH Zurich, 8093 Zurich, Switzerland.
* These authors contributed equally to this work.
Present address: Department of Chemistry, Columbia University, New York, NY 10027, USA.
To whom correspondence should be addressed. E-mail: beme{at}ethz.ch
