Reports

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

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Ultrasonication-dependent production and breakdown lead to minimum-sized amyloid fibrils.

E. Chatani, Y.-H. Lee, H. Yagi, Y. Yoshimura, H. Naiki, and Y. Goto (2009)
PNAS 106, 11119-11124
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Driving amyloid toxicity in a yeast model by structural changes: a molecular approach.

K. Berthelot, F. Immel, J. Gean, S. Lecomte, R. Oda, B. Kauffmann, and C. Cullin (2009)
FASEB J 23, 2254-2263
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Heterologous Stacking of Prion Protein Peptides Reveals Structural Details of Fibrils and Facilitates Complete Inhibition of Fibril Growth.

R. S. Boshuizen, V. Schulz, M. Morbin, G. Mazzoleni, R. H. Meloen, and J. P. M. Langedijk (2009)
J. Biol. Chem. 284, 12809-12820
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Molecular structural basis for polymorphism in Alzheimer's {beta}-amyloid fibrils.

A. K. Paravastu, R. D. Leapman, W.-M. Yau, and R. Tycko (2008)
PNAS 105, 18349-18354
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Paramagnetic shifts in solid-state NMR of proteins to elicit structural information.

S. Balayssac, I. Bertini, A. Bhaumik, M. Lelli, and C. Luchinat (2008)
PNAS 105, 17284-17289
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From the Cover: Strain-specific sequences required for yeast [PSI+] prion propagation.

H.-Y. Chang, J.-Y. Lin, H.-C. Lee, H.-L. Wang, and C.-Y. King (2008)
PNAS 105, 13345-13350
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