| Abstract
| - The contributions of interstrand side chain−side chain contacts to β-sheet stability have been examinedwith an autonomously folding β-hairpin model system. RYVEVDPGOKILQ-NH2 (DP = d-proline, O =ornithine) has previously been shown to adopt a β-hairpin conformation in aqueous solution, with a two-residue loop at d-Pro-Gly. In the present study, side chains that display interstrand NOEs (Tyr-2, Lys-9, andLeu-11) are mutated to alanine or serine, and the conformational impact of the mutations is assessed. In theβ-hairpin conformation Tyr-2 and Leu-11 are directly across from one another (non-hydrogen bonded pair).This “lateral” juxtaposition of two hydrophobic side chains appears to contribute to β-hairpin conformationalstability, which is consistent with results from other β-sheet model studies and with statistical analyses ofinterstrand residue contacts in protein crystal structures. Interaction between the side chains of Tyr-2 andLys-9 also stabilizes the β-hairpin conformation. Tyr-2/Lys-9 is a “diagonal” interstrand juxtaposition becausethese residues are not directly across from one another in terms of the hydrogen bonding registry between thestrands. This diagonal interaction arises from the right-handed twist that is commonly observed among β-sheets.Evidence of diagonal side chain−side chain contacts has been observed in other autonomously folding β-sheetmodel systems, but we are not aware of other efforts to determine whether a diagonal interaction contributesto β-sheet stability.
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