title: Effect of charged amino acid side chain length on lateral cross-strand interactions between carboxylate-containing residues and lysine analogues in a β-hairpin.
abstract: β-Sheets are one of the fundamental three-dimensional building blocks for protein structures. Oppositely charged amino acids are frequently observed directly across one another in antiparallel sheet structures, suggesting the importance of cross-strand ion pairing interactions. Despite the apparent electrostatic nature of ion pairing interactions, the charged amino acids Asp, Glu, Arg, Lys have different numbers of hydrophobic methylenes linking the charged functionality to the backbone. Accordingly, the effect of charged amino acid side chain length on cross-strand ion pairing interactions at lateral non-hydrogen bonded positions was investigated in a β-hairpin motif. The negatively charged residues with a carboxylate (Asp, Glu, Aad in increasing length) were incorporated at position 4, and the positively charged residues with an ammonium (Dap, Dab, Orn, Lys in increasing length) were incorporated at position 9. The fraction folded population and folding free energy were derived from the chemical shift deviation data. Double mutant cycle analysis was used to determine the interaction energy for the potential lateral ion pairs. Only the Asp/Glu-Dap interactions with shorter side chains and the Aad-Orn/Lys interactions with longer side chains exhibited stabilizing energetics, mostly relying on electrostatics and hydrophobics, respectively. This suggested the need for length matching of the interacting residues to stabilize the β-hairpin motif. A survey of a nonredundant protein structure database revealed that the statistical sheet pair propensity followed the trend Asp-Lys < Glu-Lys, also implying the need for length matching of the oppositely charged residues.
authors: Department of Chemistry, National Taiwan University , Taipei 10617, Taiwan.
authors: Hsiou-Ting
authors: HT
authors: Kuo
authors: Chun-Jen
authors: CJ
authors: Fang
authors: Hsin-Yun
authors: HY
authors: Tsai
authors: Min-Fan
authors: MF
authors: Yang
authors: Hsien-Chen
authors: HC
authors: Chang
authors: Shing-Lung
authors: SL
authors: Liu
authors: Li-Hung
authors: LH
authors: Kuo
authors: Wei-Ren
authors: WR
authors: Wang
authors: Po-An
authors: PA
authors: Yang
authors: Shing-Jong
authors: SJ
authors: Huang
authors: Shou-Ling
authors: SL
authors: Huang
authors: Richard P
authors: RP
authors: Cheng
mesh_terms: D024342:Amino Acids, Acidic / Q000737:chemistry*; D024361:Amino Acids, Basic / Q000737:chemistry*; D030562:Databases, Protein; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D055672:Static Electricity
chemical_list: D024342:Amino Acids, Acidic; D024361:Amino Acids, Basic; D050505:Mutant Proteins; D009842:Oligopeptides; D010455:Peptides; D008239:Lysine