title: Effect of charged amino acid side chain length at non-hydrogen bonded strand positions on β-hairpin stability.
abstract: β-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 β-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.
authors.affiliation: Department of Chemistry, National Taiwan University , Taipei 10617, Taiwan.
authors.forename: Li-Hung
authors.initials: LH
authors.lastname: Kuo
authors.forename: Jhe-Hao
authors.initials: JH
authors.lastname: Li
authors.forename: Hsiou-Ting
authors.initials: HT
authors.lastname: Kuo
authors.forename: Cheng-Yun
authors.initials: CY
authors.lastname: Hung
authors.forename: Hsin-Yun
authors.initials: HY
authors.lastname: Tsai
authors.forename: Wen-Chieh
authors.initials: WC
authors.lastname: Chiu
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Wu
authors.forename: Wei-Ren
authors.initials: WR
authors.lastname: Wang
authors.forename: Po-An
authors.initials: PA
authors.lastname: Yang
authors.forename: Yun-Chiao
authors.initials: YC
authors.lastname: Yao
authors.forename: Tong Wai
authors.initials: TW
authors.lastname: Wong
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Huang
authors.forename: Shou-Ling
authors.initials: SL
authors.lastname: Huang
authors.forename: Richard P
authors.initials: RP
authors.lastname: Cheng
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D010455:Peptides; D011506:Proteins