Biophysical and structural characterization of a robust octameric β-peptide bundle
Biophysical and structural characterization of a robust octameric β-peptide bundle
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DOI：
10.1021/ja0754002
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发表时间：
2007-11-28
影响因子：
15
通讯作者：
Schepartz, Alanna
中科院分区：
文献类型：
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作者：
Goodman, Jessica L.;Petersson, E. James;Schepartz, Alanna
由α-氨基酸组成的蛋白质是生命所需的机械的重要组成部分。斯坦利·米勒著名的放电实验提供了证据，证明甲烷、氨、水和氢的环境足以产生α-氨基酸。这一反应还产生了其他潜在的蛋白质构建单元，如β-氨基酸β-甘氨酸(也称为β-丙氨酸)；然而，这些物种形成支持功能角色的复杂有序结构的潜力尚未得到广泛研究。在这份报告中，我们应用了各种生物物理技术，包括圆二色谱、差示扫描量热法、分析超速离心法、核磁共振和X射线结晶学，来表征两个12聚体β(3)-多肽-酸-1Y和酸-1Y*的齐聚反应。与先前报道的β(3)-肽Zwit-1F一样，ACID-1Y和ACID-1Y*自发折叠成离散的八聚体四元结构，我们称之为β-肽束。令人惊讶的是，就热力学和去折叠动力学而言，酸-1Y八聚体比类似的ZWIT-1F八聚体更稳定。酸-1Y的结构，在这里报告了2.3埃的分辨率，为稳定性的增加提供了有趣的假设。综上所述，在这项工作中，我们提供了更多的证据，证明非天然的β-肽低聚物可以组装成协同折叠的结构，这在酶设计以及作为医学工具和纳米材料方面具有潜在的应用。此外，这些研究表明，自然界对α-氨基酸前体的选择不仅仅是基于它们组装成稳定低聚结构的能力。
Proteins composed of alpha-amino acids are essential components of the machinery required for life. Stanley Miller's renowned electric discharge experiment provided evidence that an environment of methane, ammonia, water, and hydrogen was sufficient to produce alpha-amino acids. This reaction also generated other potential protein building blocks such as the beta-amino acid beta-glycine (also known as beta-alanine); however, the potential of these species to form complex ordered structures that support functional roles has not been widely investigated. In this report we apply a variety of biophysical techniques, including circular dichroism, differential scanning calorimetry, analytical ultracentrifugation, NMR and X-ray crystallography, to characterize the oligomerization of two 12-mer beta(3)-peptides, Acid-1Y and Acid-1Y*. Like the previously reported beta(3)-peptide Zwit-1F, Acid-1Y and Acid-1Y* fold spontaneously into discrete, octameric quaternary structures that we refer to as beta-peptide bundles. Surprisingly, the Acid-1Y octamer is more stable than the analogous Zwit-1F octamer, in terms of both its thermodynamics and kinetics of unfolding. The structure of Acid-1Y, reported here to 2.3 angstrom resolution, provides intriguing hypotheses for the increase in stability. To summarize, in this work we provide additional evidence that nonnatural beta-peptide oligomers can assemble into cooperatively folded structures with potential application in enzyme design, and as medical tools and nanomaterials. Furthermore, these studies suggest that nature's selection of a.-amino acid precursors was not based solely on their ability to assemble into stable oligomeric structures.