Effect of Charged Amino Acid Side Chain Length at Non-Hydrogen Bonded Strand Positions on 尾-Hairpin Stability

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• 作者：Li-Hung Kuo ; Jhe-Hao Li ; Hsiou-Ting Kuo ; Cheng-Yun Hung ; Hsin-Yun Tsai ; Wen-Chieh Chiu ; Cheng-Hsun Wu ; Wei-Ren Wang ; Po-An Yang ; Yun-Chiao Yao ; Tong Wai Wong ; Shing-Jong Huang ; Shou-Ling Huang ; Richard P. Cheng
• 刊名：Biochemistry
• 出版年：2013
• 出版时间：November 5, 2013
• 年：2013
• 卷：52
• 期：44
• 页码：7785-7797
• 全文大小：559K
• 年卷期：v.52,no.44(November 5, 2013)
• ISSN：1520-4995

文摘

尾-Sheets have been implicated in various neurological disorders, and 20% of protein residues adopt a sheet conformation. Therefore, studies on the structural origin of sheet stability can provide fundamental knowledge with potential biomedical applications. Oppositely charged amino acids are frequently observed across one another in antiparallel 尾-sheets. Interestingly, the side chains of natural charged amino acids Asp, Glu, Arg, Lys have different numbers of hydrophobic methylenes linking the backbone to the hydrophilic charged functionalities. To explore the inherent effect of charged amino acid side chain length on antiparallel sheets, the stability of a designed hairpin motif containing charged amino acids with varying side chain lengths at non-hydrogen bonded positions was studied. Peptides with the guest position on the N-terminal strand and the C-terminal strand were investigated by NMR methods. The charged amino acids (Xaa) included negatively charged residues with a carboxylate group (Asp, Glu, Aad in increasing length), positively charged residues with an ammonium group (Dap, Dab, Orn, Lys in increasing length), and positively charged residues with a guanidinium group (Agp, Agb, Arg, Agh in increasing length). The fraction folded and folding free energy for each peptide were derived from the chemical shift deviation data. The stability of the peptides with the charged residues at the N-terminal guest position followed the trends: Asp > Glu > Aad, Dap < Dab < Orn Lys, and Agb < Arg < Agh < Agp. The stability of the peptides with the charged residues at the C-terminal guest position followed the trends: Asp < Glu < Aad, Dap Dab < Orn Lys, and Agb < Arg Agp < Agh. These trends were rationalized by thermodynamic sheet propensity and cross-strand interactions.