Molecular conformation of a peptide fragment of transthyretin in an amyloid fibril

The molecular conformation of peptide fragment 105-115 of transthyretin, TTR(105-115), previously shown to form amyloid fibrils in vitro, has been determined by magic-angle spinning solid-state NMR spectroscopy. C-13 and N-15 linewidth measurements indicate that TTR(105-115) forms a highly ordered structure with each amino acid in a unique environment. 2D (CC)-C-13-C-13 and N-15-C-13-C-13 chemical shift correlation experiments, performed on three fibril samples uniformly C-13,N-15-labeled in consecutive stretches of 4 aa, allowed the complete sequence-specific backbone and side-chain C-13 and N-15 resonance assignments to be obtained for residues 105-114. Analysis of the N-15, (CO)-C-13, C-13(alpha), and C-13(beta) chemical shifts allowed quantitative predictions to be made for the backbone torsion angles phi and psi. Furthermore, four backbone C-13-N-15 distances were determined in two selectively C-13,N-15-labeled fibril samples by using rotational-echo double-resonance NMR. The results show that TTR(105-115) adopts an extended beta-strand conformation that is similar to that found in the native protein except for substantial differences in the vicinity of the proline residue.