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PMID: 9811813 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Propagating structure of Alzheimer's beta-amyloid(10-35) is parallel beta-sheet with residues in exact register.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 23 ·1998-11-10 ·Pages 13407-12

Benzinger TL, Gregory DM, Burkoth TS, Miller-Auer H, Lynn DG, Botto RE, Meredith SC

Abstract

The pathognomonic plaques of Alzheimer's disease are composed primarily of the 39- to 43-aa beta-amyloid (Abeta) peptide. Crosslinking of Abeta peptides by tissue transglutaminase (tTg) indicates that Gln15 of one peptide is proximate to Lys16 of another in aggregated Abeta. Here we report how the fibril structure is resolved by mapping interstrand distances in this core region of the Abeta peptide chain with solid-state NMR. Isotopic substitution provides the source points for measuring distances in aggregated Abeta. 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 A. Analysis of these data establish that this central core of Abeta 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 Abeta fibril is a hydrogen-bonded, parallel beta-sheet defining the long axis of the Abeta fibril propagation.

MeSH Terms
Alzheimer Disease/metabolism Amino Acid Sequence Amyloid beta-Peptides/chemistry,genetics Humans Magnetic Resonance Spectroscopy Molecular Sequence Data Protein Folding Sequence Alignment
Chemicals
Amyloid beta-Peptides
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Benzinger T L
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Gregory D M
Burkoth T S
Miller-Auer H
Lynn D G
Botto R E
Meredith S C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.23.13407
Published
1998-11-10
Pages
13407-12
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24832
Subset
IM
Grants
NCRR NIH HHS · R21 RR 12723 · United States
NIGMS NIH HHS · 5 T32 GM07281 · United States
NIGMS NIH HHS · T32 GM007281 · United States
NHLBI NIH HHS · 5 T32 HL07327 · United States
NICHD NIH HHS · T32 HD007327 · United States
External Links
PubMed source DOI: 10.1073/pnas.95.23.13407 PMC Full Text View journal details
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