Site-specific structure of A¦Â(25-35) peptide: Isotope-assisted vibrational circular dichroism study

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• 作者：Ganesh Shanmugam^a ; ^b ; Prasad L. Polavarapu^a ; ^{Prasad.L.Polavarapu@Vanderbilt.edu}
• 关键词：Amyloid ; Beta sheet ; Vibrational ; Circular dichroism ; Infrared ; Isotope
• 刊名：Biochimica et Biophysica Acta - Proteins and Proteomics
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：1834
• 期：1
• 页码：308-316
• 全文大小：1190 K

文摘

We investigated the site-specific local structure of an amyloid peptide, NH₂-GSNKGAIIGLM-COOH [A¦Â(25-35)], one of the active fragments of amyloid ¦Â 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 A¦Â(25-35) peptide, along with doubly ¹³C labeled peptides at the carbonyl groups of residues 29 (Gly) and 30 (Ala) [A¦Â(25-35:¹³C-29/30)] and at the carbonyl groups of residues 33 (Gly) and 34 (Leu) [A¦Â(25-35:¹³C-33/34)]. The present results confirm that A¦Â(25-35) peptide fibrils adopt a ¦Â-sheet structure and isotopic dilution experiments suggest a parallel ¦Â-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¡ä VCD intensities of A¦Â(25-35:¹³C-29/30) and A¦Â(25-35:¹³C-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.