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.

^{α-螺旋在结构生物学1}中表现突出，并在蛋白质折叠²、设计³和工程⁴中得到广泛利用。尽管其他螺旋肽构象确实存在于构象空间的 α-螺旋区域附近——即 3_{个 10-}螺旋和 π-螺旋^5——它们在蛋白质结构中的出现频率要低得多。不太有利的内部能量和减少进入高阶结构的趋势意味着 3 ₁₀- 在天然蛋白质中，螺旋的长度很少超过六个残基，并且它们往往不会形成正常的超二级、三级或四级相互作用。在这里，我们表明尽管它们在自然界中不存在，但可以从 3_{个 10} -螺旋构建合成肽组件。我们报告了具有固结疏水核心的 3_{个 10-}螺旋水溶性束的合理设计、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 3个 10}螺旋构象获得的六残基重复序列，并结合了 α-氨基异丁酸残基。_{设计迭代揭示了 α 螺旋和 3 10}之间的转折点-螺旋折叠，并确定稳定 3_{个 10} -螺旋组件所需的特征。这项工作提供了原则和规则，为设计这个迄今为止尚未探索的蛋白质结构空间区域提供了机会。