title: Effect of charged amino acid side chain length on lateral cross-strand interactions between carboxylate- and guanidinium-containing residues in a β-hairpin.
abstract: β-Sheet is one of the major protein secondary structures. Oppositely charged residues are frequently observed across neighboring strands in antiparallel sheets, suggesting the importance of cross-strand ion pairing interactions. The charged amino acids Asp, Glu, Arg, and Lys have different numbers of hydrophobic methylenes linking the charged functionality to the backbone. To investigate the effect of side chain length of guanidinium- and carboxylate-containing residues on lateral cross-strand ion pairing interactions at non-hydrogen-bonded positions, β-hairpin peptides containing Zbb-Agx (Zbb = Asp, Glu, Aad in increasing length; Agx = Agh, Arg, Agb, Agp in decreasing length) sequence patterns were studied by NMR methods. The fraction folded population and folding energy were derived from the chemical shift deviation data. Peptides with high fraction folded populations involved charged residue side chain lengths that supported high strand propensity. Double mutant cycle analysis was used to determine the interaction energy for the potential lateral ion pairs. Minimal interaction was observed between residues with short side chains, most likely due to the diffused positive charge on the guanidinium group, which weakened cross-strand electrostatic interactions with the carboxylate side chain. Only the Aad-Arg/Agh interactions with long side chains clearly exhibited stabilizing energetics, possibly relying on hydrophobics. A survey of a non-redundant protein structure database revealed that the statistical sheet pair propensity followed the trend Asp-Arg < Glu-Arg, implying the need for matching long side chains. This suggested the need for long side chains on both guanidinium-bearing and carboxylate-bearing residues to stabilize the β-hairpin motif.
authors: Department of Chemistry, National Taiwan University, Taipei, 10617, Taiwan.
authors: Hsiou-Ting
authors: HT
authors: Kuo
authors: Shing-Lung
authors: SL
authors: Liu
authors: Wen-Chieh
authors: WC
authors: Chiu
authors: Chun-Jen
authors: CJ
authors: Fang
authors: Hsien-Chen
authors: HC
authors: Chang
authors: Wei-Ren
authors: WR
authors: Wang
authors: Po-An
authors: PA
authors: Yang
authors: Jhe-Hao
authors: JH
authors: Li
authors: Shing-Jong
authors: SJ
authors: Huang
authors: Shou-Ling
authors: SL
authors: Huang
authors: Richard P
authors: RP
authors: Cheng
mesh_terms: D015074:2-Aminoadipic Acid / Q000737:chemistry*; D000409:Alanine / Q000737:chemistry; D001120:Arginine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*; D030562:Databases, Protein; D018698:Glutamic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*; D006146:Guanidines / Q000737:chemistry*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008239:Lysine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D006146:Guanidines; D015074:2-Aminoadipic Acid; D001224:Aspartic Acid; D018698:Glutamic Acid; D001120:Arginine; D008239:Lysine; D000409:Alanine