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Cooperative folding of tau peptide by coordination of group IIB metal cations during heparin-induced aggregation.
MedLine Citation:
PMID:  22083130     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The group IIB elements, especially Cd(II) and Hg(II), are increasingly considered as potential environmental neurotoxins. This study demonstrates that the Alzheimer's tau fragment R2, corresponding to the second repeat of the microtubule-binding domain, can bind to Zn(II), Cd(II) and Hg(II). Isothermal titration calorimetry experiments suggest that the most likely coordination site is the thiol group of Cys291, and this is further confirmed by a control experiment using a C291A mutant peptide. Circular dichroism spectrum reveals that the coordination of group IIB cations, especially Hg(II), can induce pronounced conformational conversions in natively unfolded R2, from random coil to other ordered structures. ThS fluorescence assays and electron microscopy indicate that the group IIB cations promote heparin-induced aggregation of R2, giving relatively small R2 filaments. The efficiency in promoting aggregation, as well as inducing conformational conversion, varies strongly with the cation's polarizability. Based on these results, a model is proposed in which the cooperative folding of R2 through cross-bridging of group IIB cations is suggested to be a key factor in promoting aggregation, in addition to the effective neutralization of coulombic charge-charge repulsion by heparin, the poly-anion inducer. Our results provide clues to understanding the potential pathogenic role of group IIB metals in the development of neurofibrillary tangles, a typical hallmark of Alzheimer's disease.
Authors:
Dan-Jing Yang; Shuo Shi; Tian-Ming Yao; Liang-Nian Ji
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-15
Journal Detail:
Title:  Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine     Volume:  -     ISSN:  1572-8773     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9208478     Medline TA:  Biometals     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Chemistry, Tongji University, 1239 Siping Road, Shanghai, 200092, China.
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