Atomic-Resolution Three-Dimensional Structure of HET-s(218-289) Amyloid Fibrils by Solid-State NMR Spectroscopy

作者：Van Melckebeke Helene; Wasmer Christian; Lange Adam; AB Eiso; Loquet Antoine; Bockmann Anja; Meier Beat H^*

来源：Journal of the American Chemical Society, 2010, 132(39): 13765-13775.

DOI：10.1021/ja104213J

We present a strategy to solve the high-resolution structure of amyloid fibrils by solid-state NMR and use it to determine the atomic-resolution structure of the prion domain of the fungal priori HET-s in its amyloid form. On the basis of 134 unambiguous distance restraints, we recently showed that HETs-(218-289) in its fibrillar state forms a left-handed beta-solenoid, and an atomic-resolution NMR structure of the triangular core was determined from unambiguous restraints only. In this paper, we go considerably further and present a comprehensive protocol using six differently labeled samples, a collection of optimized solid-state NMR experiments, and adapted structure calculation protocols. The high-resolution structure obtained includes the less ordered but biologically important C-terminal part and improves the overall accuracy by including a large number of ambiguous distance restraints.

• 出版日期2010-10-6