Propagating structure of alzheimer's {beta}-amyloid is parallel {beta}-sheet with residues in exact register.
The pathognomonic plaques of Alzheimer's disease are composed primarily of the 39- to 43-aa {beta}-amyloid (A{beta}) peptide. Crosslinking of A{beta} peptides by tissue transglutaminase (tTg) indicates that Gln15 of one peptide is proximate to Lys16 of another in aggregated A{beta}. Here we report how the fibril structure is resolved by mapping interstrand distances in this core region of the A{beta} peptide chain with solid-state NMR. Isotopic substitution provides the source points for measuring distances in aggregated A{beta}. Peptides containing a single carbonyl 13C label at Gln15, Lys16, Leu17, or Val18 were synthesized and evaluated by NMR dipolar recoupling methods for the measurement of interpeptide distances to a resolution of 0.2 Angstrom. Analysis of these data establish that this central core of A{beta} consists of a parallel {beta}-sheet structure in which identical residues on adjacent chains are aligned directly, i.e., in register. Our data, in conjunction with existing structural data, establish that the A{beta} fibril is a hydrogen-bonded, parallel {beta}-sheet defining the long axis of the A{beta} fibril propagation.
- Research Organization:
- Argonne National Laboratory (ANL)
- Sponsoring Organization:
- ER
- DOE Contract Number:
- AC02-06CH11357
- OSTI ID:
- 938398
- Report Number(s):
- ANL/CHM/JA-30162
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A., Journal Name: Proc. Natl. Acad. Sci. U.S.A. Journal Issue: 23 ; Nov. 10, 1998 Vol. 95; ISSN PNASA6; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- ENGLISH
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