Insights on beta-hairpin stability in aqueous solution from peptides with enforced type I' and type II' beta-turns
Insights on beta-hairpin stability in aqueous solution from peptides with enforced type I' and type II' beta-turns
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DOI：
10.1021/ja963653h
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发表时间：
1997-03-05
影响因子：
15
通讯作者：
Gellman, SH
中科院分区：
文献类型：
--
作者：
Haque, TS;Gellman, SH
R-螺旋2和β-转角3的稳定性，但这种方法难以对β-折叠实施。4个β-发夹结构包含两个反向平行的β-链，通过一个短环连接，构成β-折叠的最小增量，因此可以为探测反向平行β-折叠的稳定性提供基础。5-9在这里，我们表明，在一个家庭的16个残基肽的选择性D-残基掺入诱导β-发夹折叠，在一个确定的位置，在水溶液中的紧密的两个残基的环。这些异手性肽与全-L非对映体的比较提供了有利于β-发夹构象的力的洞察。最近已经显示了几种短肽在水溶液中采用β-发夹构象，5-8但是使用这些肽作为β-折叠分析的平台是有问题的，因为指定环的位置和大小的因素还不清楚。第一个报道的自主发夹，YQNPDGSQA（1），是通过从tendamistat的残基15-23，YQSWRYSQA外推设计的。5a在1中，PDG片段形成三残基环，5a但天然蛋白中的原始序列在WR片段处采用具有两残基环的β-发夹。10 Searle等人在MQIFVKNPDGTLTLEV-NH 2中发现了β-发夹折叠（2），7这是一种源自泛素MQIFVKTLTGKTITLEV的17个N-末端残基的16个残基的肽。在天然蛋白质中，这17个残基采用具有跨越LTG的三残基环的β-发夹。11 Searle等人打算用一个紧密的、跨PD的两个残基的环来替换这个天然环;然而，2形成了一个具有跨PDG的三个残基的环的β-发夹，这导致了非天然链配对。7
R-helix 2 and β-turn3 stability, but this approach has been difficult to implement for a β-sheet. 4 β-Hairpins, which contain two antiparallel β-strands linked by a short loop, constitute minimum increments of a β-sheet and therefore could provide a basis for probing antiparallel β-sheet stability. 5-9 Here, we show that selective D-residue incorporation in a family of 16-residue peptides induces β-hairpin folding, with a tight two-residue loop at a defined position, in aqueous solution. Comparison of these heterochiral peptides with the all-L diastereomers provides insight on the forces that favor the β-hairpin conformation.Several short peptides have recently been shown to adopt β-hairpin conformations in aqueous solution, 5-8 but the use of these peptides as platforms for β-sheet analysis is problematic because the factors that specify the position and size of the loop have been unclear. The first reported autonomous hairpin, YQNPDGSQA (1), was designed by extrapolation from residues 15-23 of tendamistat, YQSWRYSQA. 5a In 1, the PDG segment forms a three-residue loop, 5a but the original sequence in the native protein adopts a β-hairpin with a two-residue loop at the WR segment. 10 Searle et al. have found β-hairpin folding in MQIFVKNPDGTLTLEV-NH2 (2), 7 a 16-residue peptide derived from the 17 N-terminal residues of ubiquitin, MQIFVKTLTGKTITLEV. In the native protein, these 17 residues adopt a β-hairpin with a three-residue loop across LTG. 11 Searle et al. intended to replace this natural loop with a tight, two-residue loop across PD; however, 2 formed a β-hairpin with a threeresidue loop across PDG, which led to a non-native strand pairing. 7