Conformational investigation of designed short linear peptides able to fold into beta-hairpin structures in aqueous solution
Conformational investigation of designed short linear peptides able to fold into beta-hairpin structures in aqueous solution
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DOI：
10.1016/s1359-0278(96)00022-3
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发表时间：
1996-01-01
期刊：
影响因子：
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通讯作者：
Nieto, JL
中科院分区：
文献类型：
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作者：
deAlba, E;Jimenez, MA;Nieto, JL
背景：二级结构的形成在蛋白质折叠的早期阶段起着重要的作用。设计的肽的构象分析已被证明是非常有用的识别负责的α-螺旋的形成和稳定性的相互作用。然而，人们对导致β-发夹形成的因素知之甚少。为了得到良好的β-发夹形成模型肽，根据β-折叠倾向和转角位点中的个体统计概率以及溶解度标准设计了两种肽。结果：在NOE和ROE谱中观察到的长程交叉相关以及其他NMR证据表明，肽IYSNPDGTWT在水溶液中形成高度密集的β-发夹结构，在链弯曲区域具有I型β-转角和G1型β-凸起构象。具有被Ser取代的Pro 5的类似肽除了先前的构象之外还形成具有标准I型β-转角构象的第二个β-发夹，并且这两种形式彼此处于快速动态平衡。pH值的影响表明存在的稳定的相互作用之间的天冬酰胺和天冬氨酸侧链。在三氟乙醇（一种结构增强溶剂）的存在下，β-发夹构象的数量增加。另一方面，一些残留的结构仍然存在于高变性剂浓度（8 M尿素）。结论：这项工作突出了β-转残基组合物的重要性，在确定特定类型的β-发夹通过肽，虽然链间侧链相互作用的稳定形成的β-发夹的作用没有被丢弃。三氟乙醇可以稳定α-螺旋或β-发夹的事实，这取决于肽序列的内在性质再次显示。还提出了在变性条件下存在残余结构的另一个例子。
Background: Formation of secondary structure plays an important role in the early stages of protein folding. The conformational analysis of designed peptides has proved to be very useful for identifying the interactions responsible for the formation and stability of alpha-helices. However, very little is known about the factors leading to the formation of beta-hairpins. In order to get a good beta-hairpin-forming model peptide, two peptides were designed on the basis of beta-sheet propensities and individual statistical probabilities in the turn sites, together with solubility criteria. The conformational properties of the two peptides were analyzed by two-dimensional NMR methods.Results: Long-range cross-correlations observed in NOE and ROE spectra, together with other NMR evidence, show that peptide IYSNPDGTWT forms a highly populated beta-hairpin in aqueous solution with a type I beta-turn plus a G1 beta-bulge conformation in the chain-bend region. The analogous peptide with a Pro5 substituted by Ser forms, in addition to the previous conformation, a second beta-hairpin hairpin with a standard type I beta-turn conformation, and the two forms are in fast dynamic equilibrium with one another. The effect of pH demonstrates the existence of a stabilizing interaction between the Asn and Asp sidechains. The populations of beta-hairpin conformations increase in the presence of trifluoroethanol (a structure-enhancing solvent). On the other hand, some residual structure persists at a high denaturant concentration (8 M urea).Conclusions: This work highlights the importance of the beta-turn residue composition in determining the particular type of beta-hairpin adopted by a peptide, though a role of interstrand sidechain interactions in the stabilization of the formed beta-hairpin is not discarded. The fact that trifluoroethanol can stabilize alpha-helices or beta-hairpins depending on the intrinsic properties of the peptide sequence is again shown. An additional example of the presence of residual structure under denaturing conditions is also presented.