Interstrand side chain-side chain interactions in a designed β-hairpin:: Significance of both lateral and diagonal pairings
Interstrand side chain-side chain interactions in a designed β-hairpin:: Significance of both lateral and diagonal pairings
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DOI：
10.1021/ja0109803
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发表时间：
2001-09-12
影响因子：
15
通讯作者：
Gellman, SH
中科院分区：
文献类型：
--
作者：
Syud, FA;Stanger, HE;Gellman, SH
用自行折叠的β-发夹模型系统研究了链间侧链-侧链接触对β-折叠稳定性的贡献。RYVEV（D）PGOKILQ-NH 2（P-D = D-脯氨酸，O =鸟氨酸）先前已显示在水溶液中采用β-发夹构象，在D-Pro-Gly处具有两个残基环。在本研究中，显示链间NOE（Tyr-2，Lys-9和Leu-11）的侧链突变为丙氨酸或丝氨酸，并评估突变的构象影响。在β-发夹构象中，Tyr-2和Leu-11彼此直接相对（非氢键对）。两个疏水侧链的这种“横向”并置似乎有助于β-发夹构象稳定性，这与其他β-折叠模型研究的结果以及蛋白质晶体结构中链间残基接触的统计分析一致. Tyr-2和Lys-9的侧链之间的相互作用也稳定了6-发夹构象。Tyr-2/Lys-9是“对角”链间并置，因为这些残基就链之间的氢键注册而言不是直接彼此相对。这种对角相互作用来自于在ss -片层中通常观察到的右手扭曲。对角侧链-侧链接触的证据已经在其他自主折叠的β-折叠模型系统中观察到，但我们不知道其他的努力，以确定对角相互作用是否有助于β-折叠的稳定性。
The contributions of interstrand side chain-side chain contacts to ss -sheet stability have been examined with an autonomously folding ss -hairpin model system. RYVEV(D)PGOKILQ-NH2 (P-D = D-proline, O = ornithine) has previously been shown to adopt a ss -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, and Leu-11) are mutated to alanine or serine, and the conformational impact of the mutations is assessed. In the ss -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 ss -hairpin conformational stability, which is consistent with results from other ss -sheet model studies and with statistical analyses of interstrand residue contacts in protein crystal structures. Interaction between the side chains of Tyr-2 and Lys-9 also stabilizes the 6-hairpin conformation. Tyr-2/Lys-9 is a "diagonal" interstrand juxtaposition because these residues are not directly across from one another in terms of the hydrogen bonding registry between the strands. This diagonal interaction arises from the right-handed twist that is commonly observed among ss -sheets. Evidence of diagonal side chain-side chain contacts has been observed in other autonomously folding ss -sheet model systems, but we are not aware of other efforts to determine whether a diagonal interaction contributes to beta -sheet stability.