Spencer Ryan K, Hochbaum Allon I
Department of Chemistry and Department of Chemical Engineering & Materials Science, University of California, Irvine , Irvine, California 92697-2575, United States.
Biochemistry. 2016 Jun 14;55(23):3214-23. doi: 10.1021/acs.biochem.6b00201. Epub 2016 May 27.
The self-assembly of peptides and proteins into higher-ordered structures is encoded in the amino acid sequence of each peptide or protein. Understanding the relationship among the amino acid sequence, the assembly dynamics, and the structure of well-defined peptide oligomers expands the synthetic toolbox for these structures. Here, we present the X-ray crystallographic structure and solution behavior of de novo peptides that form antiparallel coiled-coil hexamers (ACC-Hex) by an interaction motif neither found in nature nor predicted by existing peptide design software. The 1.70 Å X-ray crystallographic structure of peptide 1a shows six α-helices associating in an antiparallel arrangement around a central axis comprising hydrophobic and aromatic residues. Size-exclusion chromatography studies suggest that peptides 1 form stable oligomers in solution, and circular dichroism experiments show that peptides 1 are stable to relatively high temperatures. Small-angle X-ray scattering studies of the solution behavior of peptide 1a indicate an equilibrium of dimers, hexamers, and larger aggregates in solution. The structures presented here represent a new motif of biomolecular self-assembly not previously observed for de novo peptides and suggest supramolecular design principles for material scaffolds based on coiled-coil motifs containing aromatic residues.
肽和蛋白质自组装成高阶结构是由每个肽或蛋白质的氨基酸序列编码的。了解氨基酸序列、组装动力学以及明确的肽寡聚体结构之间的关系，扩展了用于这些结构的合成工具箱。在这里，我们展示了从头合成肽的X射线晶体结构和溶液行为，这些肽通过一种在自然界中未发现且现有肽设计软件也未预测到的相互作用基序形成反平行卷曲螺旋六聚体（ACC-Hex）。肽1a的1.70 Å X射线晶体结构显示，六个α螺旋围绕由疏水和芳香族残基组成的中心轴以反平行排列方式缔合。尺寸排阻色谱研究表明，肽1在溶液中形成稳定的寡聚体，圆二色性实验表明，肽1在相对较高温度下是稳定的。肽1a溶液行为的小角X射线散射研究表明，溶液中存在二聚体、六聚体和更大聚集体的平衡。这里展示的结构代表了一种新的生物分子自组装基序，以前在从头合成肽中未观察到，并为基于含有芳香族残基的卷曲螺旋基序的材料支架提出了超分子设计原则。
