Metal Switch for Amyloid Formation:  Insight into the Structure of the Nucleus

The role of Zn2+ in pre-organizing Aβ(10−21) amyloid formation is shown to preferentially alter the relative rate of fibril nucleation and to have little influence on fibril propagation. Fibril morphology, as determined by small angle neutron scattering (SANS) and transmission electron microscopy (T...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2002-10, Vol.124 (43), p.12644-12645
Main Authors: Morgan, David M, Dong, Jijun, Jacob, Jaby, Lu, Kun, Apkarian, Robert P, Thiyagarajan, Pappannan, Lynn, David G
Format: Article
Language:English
Subjects:
Amyloid - biosynthesis
Amyloid - chemistry
Binding Sites
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Kinetics
Microscopy, Electron
Models, Molecular
Molecular biophysics
Peptide Fragments - chemistry
Structure in molecular biology
Supramolecular structure
Zinc - chemistry
Zinc - metabolism
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Summary:The role of Zn2+ in pre-organizing Aβ(10−21) amyloid formation is shown to preferentially alter the relative rate of fibril nucleation and to have little influence on fibril propagation. Fibril morphology, as determined by small angle neutron scattering (SANS) and transmission electron microscopy (TEM), was unchanged in the presence and absence of Zn2+ in Aβ(10−21), as well as in a series of site-specifically altered variants. The metal-independence of the Aβ(10−21)H13Q peptide suggested that the increase in nucleation rate in Aβ(10−21) is due to Zn2+-mediated inter-sheet interactions, involving both histidine 13 and histidine 14.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja0273086