Two-Dimensional Structure of -Amyloid(10-35) Fibrils
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- 作者：Tammie L. S. Benzinger ; David M. Gregory ; Timothy S. Burkoth ; Hé ; lè ; ne Miller-Auer ; David G. Lynn ; Robert E. Botto ; and Stephen C. Meredith
- 刊名：Biochemistry
- 出版年：2000
- 出版时间：March 28, 2000
- 年：2000
- 卷：39
- 期：12
- 页码：3491 - 3499
- 全文大小：274K
- 年卷期：v.39,no.12(March 28, 2000)
- ISSN：1520-4995
文摘
-Amyloid (A) peptides are the main protein component of the pathognomonic plaques foundin the brains of patients with Alzheimer's disease. These heterogeneous peptides adopt a highly organizedfibril structure both in vivo and in vitro. Here we use solid-state NMR on stable, homogeneous fibrils ofA(10-35). Specific interpeptide distance constraints are determined with dipolar recoupling NMR on fibrilsprepared from a series of singly labeled peptides containing 13C-carbonyl-enriched amino acids, and skippingno more that three residues in the sequence. From these studies, we demonstrate that the peptide adoptsthe structure of an extended parallel -sheet in-register at pH 7.4. Analysis of DRAWS data indicatesinterstrand distances of 5.3 ± 0.3 Å (mean ± standard deviation) throughout the entire length of thepeptide, which is compatible only with a parallel -strand in-register. Intrastrand NMR constraints, obtainedfrom peptides containing labels at two adjacent amino acids, confirm the secondary structural findingsobtained using DRAWS. Using peptides with 13C incorporated at the carbonyl position of adjacent aminoacids, structural transitions from 
-helix to -sheet were observed at residues 19 and 20, but using similartechniques, 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(10-35) for overall fibril formation, stability, andmorphology based upon specific amino acid contacts are discussed.