小柯机器人

英国布里斯托尔大学Derek N. Woolfson和Prasun Kumar共同合作，近期取得重要工作进展，他们重头设计了离散、稳定的3₁₀-螺旋肽组装体。该项研究结果2022年6月22日在线出版于《自然》杂志上。

在这里，研究人员表明，尽管它们在自然界中不存在，但合成肽组件可以由3₁₀-螺旋构建。研究人员报告了具有固结疏水核的水溶性3₁₀-螺旋束的合理设计、溶液相表征和X射线晶体结构。该设计使用通过分析已知蛋白质结构中的3₁₀螺旋构象获得六个残基重复序列，并包含α-氨基异丁酸残基。设计迭代揭示了α-螺旋和3₁₀-螺旋折叠之间的临界点，并确定了稳定3₁₀-螺旋组件所需的特征。这项工作提供了一些原则和规则，为在这个迄今为止尚未开发的蛋白质结构空间区域进行设计提供了机会。

据了解，α-螺旋在结构生物学中非常突出，在蛋白质折叠、设计和工程中得到了广泛的应用。尽管在构象空间的α-螺旋区域(即3₁₀-螺旋和π-螺旋)附近确实存在其他螺旋肽构象，但这些构象在蛋白质结构中出现的频率要低得多。不太有利的内部能量和减少堆积成高阶结构的趋势意味着天然蛋白质中3₁₀-螺旋的长度很少超过6个残基，并且它们往往不形成正常的超二级、三级或四级相互作用。

附：英文原文

Title: De novo design of discrete, stable 310-helix peptide assemblies

Author: Kumar, Prasun, Paterson, Neil G., Clayden, Jonathan, Woolfson, Derek N.

Issue&Volume: 2022-06-22

Abstract: The α-helix is pre-eminent in structural biology1 and widely exploited in protein folding2, design3 and engineering4. Although other helical peptide conformations do exist near to the α-helical region of conformational space—namely, 310-helices and π-helices5—these occur much less frequently in protein structures. Less favourable internal energies and reduced tendencies to pack into higher-order structures mean that 310-helices rarely exceed six residues in length in natural proteins, and that they tend not to form normal supersecondary, tertiary or quaternary interactions. Here we show that despite their absence in nature, synthetic peptide assemblies can be built from 310-helices. We report the rational design, solution-phase characterization and an X-ray crystal structure for water-soluble bundles of 310-helices with consolidated hydrophobic cores. The design uses six-residue repeats informed by analysing 310-helical conformations in known protein structures, and incorporates α-aminoisobutyric acid residues. Design iterations reveal a tipping point between α-helical and 310-helical folding, and identify features required for stabilizing assemblies of 310-helices. This work provides principles and rules to open opportunities for designing into this hitherto unexplored region of protein-structure space.

DOI: 10.1038/s41586-022-04868-x

Source: https://www.nature.com/articles/s41586-022-04868-x

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html