Two-dimensional structure of {beta}-Amyloid(10-35) fibrils.
{beta}-Amyloid (A{beta}) peptides are the main protein component of the pathognomonic plaques found in the brains of patients with Alzheimer's disease. These heterogeneous peptides adopt a highly organized fibril structure both in vivo and in vitro. Here we use solid-state NMR on stable, homogeneous fibrils of A{beta}{sub (10-35)}. Specific interpeptide distance constraints are determined with dipolar recoupling NMR on fibrils prepared from a series of singly labeled peptides containing {sup 13}C-carbonyl-enriched amino acids, and skipping no more than three residues in the sequence. From these studies, we demonstrate that the peptide adopts the structure of an extended parallel {beta}-sheet in-register at pH 7.4. Analysis of DRAWS data indicates interstrand distances of 5.3 {+-} 0.3 {angstrom} (mean {+-} standard deviation) throughout the entire length of the peptide, which is compatible only with a parallel {beta}-strand in-register. Intrastrand NMR constraints, obtained from peptides containing labels at two adjacent amino acids, confirm the secondary structural findings obtained using DRAWS. Using peptides with {sup 13}C incorporated at the carbonyl position of adjacent amino acids, structural transitions from {alpha}-helix to {beta}-sheet were observed at residues 19 and 20, but using similar techniques, no evidence for a turn could be found in the putative turn region comprising residues 25-29. Implications of this extended parallel organization for A{beta}{sub (10-35)} for overall fibril formation, stability, and morphology based upon specific amino acid contacts are discussed.
- Research Organization:
- Argonne National Laboratory (ANL)
- Sponsoring Organization:
- SC
- DOE Contract Number:
- AC02-06CH11357
- OSTI ID:
- 942885
- Report Number(s):
- ANL/CHM/JA-35628
- Journal Information:
- Biochemistry, Journal Name: Biochemistry Journal Issue: 12 ; Mar. 28, 2000 Vol. 39; ISSN 0006-2960; ISSN BICHAW
- Country of Publication:
- United States
- Language:
- ENGLISH
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