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. 13C and 15N linewidth measurements indicate that TTR(105-115) forms a highly ordered structure with each amino acid in a unique environment. 2D 13C-13C and 15N-13C-13C chemical shift correlation experiments, performed on three fibril samples uniformly 13C,15N-labeled in consecutive stretches of 4 aa, allowed the complete sequence-specific backbone and side-chain 13C and 15N resonance assignments to be obtained for residues 105-114. Analysis of the 15N, 13CO, 13Calpha, and 13Cbeta chemical shifts allowed quantitative predictions to be made for the backbone torsion angles phi and psi. Furthermore, four backbone 13C-15N distances were determined in two selectively 13C,15N-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.
Jaroniec
Christopher P
CP
Department of Chemistry and Center for Magnetic Resonance, Francis Bitter Magnet Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
MacPhee
Cait E
CE
Astrof
Nathan S
NS
Dobson
Christopher M
CM
Griffin
Robert G
RG
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D006801:Humans; D008854:Microscopy, Electron; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry*; D011228:Prealbumin / Q000737:chemistry*; D011487:Protein Conformation
D000682:Amyloid; D010446:Peptide Fragments; D011228:Prealbumin