Effect of charged amino acid side chain length on lateral cross-strand interactions between carboxylate- and guanidinium-containing residues in a β-hairpin

摘要: β-Sheet is one of the major protein secondary structures. Oppositely charged residues are frequently observed across neighboring strands in antiparallel sheets, suggesting importance cross-strand ion pairing interactions. The amino acids Asp, Glu, Arg, and Lys have different numbers hydrophobic methylenes linking functionality to backbone. To investigate effect side chain length guanidinium- carboxylate-containing on lateral interactions at non-hydrogen-bonded positions, β-hairpin peptides containing Zbb-Agx (Zbb = Aad increasing length; Agx Agh, Agb, Agp decreasing length) sequence patterns were studied by NMR methods. fraction folded population folding energy derived from chemical shift deviation data. Peptides with high populations involved residue lengths that supported strand propensity. Double mutant cycle analysis was used determine interaction for potential pairs. Minimal between short chains, most likely due diffused positive charge guanidinium group, which weakened electrostatic carboxylate chain. Only Aad-Arg/Agh long chains clearly exhibited stabilizing energetics, possibly relying hydrophobics. A survey a non-redundant structure database revealed statistical sheet pair propensity followed trend Asp-Arg < Glu-Arg, implying need matching chains. This suggested both guanidinium-bearing carboxylate-bearing stabilize motif.