de Alba E, Rico M, Jiménez M A
Instituto de Estructura de la Materia, Consejo Superior de Investigaciones Cientifícas, Madrid, Spain.
Protein Sci. 1997 Dec;6(12):2548-60. doi: 10.1002/pro.5560061207.
A series of designed peptides has been analyzed by 1H-NMR spectroscopy in order to investigate the influence of cross-strand side-chain interactions in beta-hairpin formation. The peptides differ in the N-terminal residues of a previously designed linear decapeptide that folds in aqueous solution into two interconverting beta-hairpin conformations, one with a type I turn (beta-hairpin 4:4) and the other with a type I + G1 beta-bulge turn (beta-hairpin 3:5). Analysis of the conformational behavior of the peptides studied here demonstrates three favorable and two unfavorable cross-strand side-chain interactions for beta-hairpin formation. These results are in agreement with statistical data on side-chain interactions in protein beta-sheets. All the peptides in this study form significant populations of the beta-hairpin 3:5, but only some of them also adopt the beta-hairpin 4:4. The formation of beta-hairpin 4:4 requires the presence of at least two favorable cross-strand interactions, whereas beta-hairpin 3:5 seems to be less susceptible to side-chain interactions. A protein database analysis of beta-hairpins 3:5 and beta-hairpins 4:4 indicates that the former occur more frequently than the latter. In both peptides and proteins, beta-hairpins 3:5 have a larger right-handed twist than beta-hairpins 4:4, so that a factor contributing to the higher stability of beta-hairpin 3:5 relative to beta-hairpin 4:4 is due to an appropriate backbone conformation of the type I + G1 beta-bulge turn toward the right-handed twist usually observed in protein beta-sheets. In contrast, as suggested previously, backbone geometry of the type I turn is not adequate for the right-handed twist. Because analysis of buried hydrophobic surface areas on protein beta-hairpins reveals that beta-hairpins 3:5 bury more hydrophobic surface area than beta-hairpins 4:4, we suggest that the right-handed twist observed in beta-hairpin 3:5 allows a better packing of side chains and that this may also contribute to its higher intrinsic stability.
为了研究β-发夹结构形成过程中跨链侧链相互作用的影响，通过1H-NMR光谱对一系列设计的肽进行了分析。这些肽在先前设计的线性十肽的N端残基上有所不同，该线性十肽在水溶液中折叠成两种相互转化的β-发夹构象，一种具有I型转角（β-发夹4:4），另一种具有I + G1β-凸起转角（β-发夹3:5）。对这里研究的肽的构象行为分析表明，对于β-发夹结构的形成，存在三种有利和两种不利的跨链侧链相互作用。这些结果与蛋白质β-折叠中侧链相互作用的统计数据一致。本研究中的所有肽都形成了大量的β-发夹3:5，但只有其中一些也采用β-发夹4:4。β-发夹4:4的形成需要至少存在两种有利的跨链相互作用，而β-发夹3:5似乎对侧链相互作用不太敏感。对β-发夹3:5和β-发夹4:4的蛋白质数据库分析表明，前者比后者出现得更频繁。在肽和蛋白质中，β-发夹3:5比β-发夹4:4具有更大的右手扭转，因此β-发夹3:5相对于β-发夹4:4具有更高稳定性的一个因素是I + G1β-凸起转角的合适主链构象朝向蛋白质β-折叠中通常观察到的右手扭转。相比之下，如先前所述，I型转角的主链几何形状不适合右手扭转。因为对蛋白质β-发夹上埋藏的疏水表面积的分析表明，β-发夹3:5比β-发夹4:4埋藏更多的疏水表面积，我们认为在β-发夹3:5中观察到的右手扭转允许侧链更好地堆积，这也可能有助于其更高的内在稳定性。
