Document Detail


Site-specific structure of Aβ(25-35) peptide: Isotope-assisted vibrational circular dichroism study.
MedLine Citation:
PMID:  22910376     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
We investigated the site-specific local structure of an amyloid peptide, NH(2)-GSNKGAIIGLM-COOH [Aβ(25-35)], one of the active fragments of amyloid β peptide that is known to be responsible for Alzheimer's disease, in the fibrillar aggregated state. Isotope-assisted infrared vibrational circular dichroism (VCD) and absorption (VA) spectroscopy were used for the parent Aβ(25-35) peptide, along with doubly (13)C labeled peptides at the carbonyl groups of residues 29 (Gly) and 30 (Ala) [Aβ(25-35:(13)C-29/30)] and at the carbonyl groups of residues 33 (Gly) and 34 (Leu) [Aβ(25-35:(13)C-33/34)]. The present results confirm that Aβ(25-35) peptide fibrils adopt a β-sheet structure and isotopic dilution experiments suggest a parallel β-sheet structure. The isotopic shifts suggest that the microenvironment of residues 29 (Gly) and 30 (Ala) could be different from that of residues 33 (Gly) and 34 (Leu). An unusual enhancement for the amide II' VCD intensities of Aβ(25-35:(13)C-29/30) and Aβ(25-35:(13)C-33/34) peptide fibrils, considered to originate from inter-strand coupling, was found for the first time. The structural information reported in this manuscript has important implications in understanding the role of this peptide in the development of Alzheimer's disease.
Authors:
Ganesh Shanmugam; Prasad L Polavarapu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-15
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  -     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA; Bioorganic Laboratory, CSIR-Central Leather Research Institute, Adyar, Chennai, 600 020 India.
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