Department of Chemistry, Brandeis University, 415 South St., Waltham, MA 02453, USA.
Molecules. 2020 Dec 26;26(1):77. doi: 10.3390/molecules26010077.
The advance of structural biology has revealed numerous noncovalent interactions between peptide sequences in protein structures, but such information is less explored for developing peptide materials. Here we report the formation of heterotypic peptide hydrogels by the two binding motifs revealed by the structures of an inflammasome. Specifically, conjugating a self-assembling motif to the positively or negatively charged peptide sequence from the ASCPYD filaments of inflammasome produces the solutions of the peptides. The addition of the peptides of the oppositely charged and complementary peptides to the corresponding peptide solution produces the heterotypic hydrogels. Rheology measurement shows that ratios of the complementary peptides affect the viscoelasticity of the resulted hydrogel. Circular dichroism indicates that the addition of the complementary peptides results in electrostatic interactions that modulate self-assembly. Transmission electron microscopy reveals that the ratio of the complementary peptides controls the morphology of the heterotypic peptide assemblies. This work illustrates a rational, biomimetic approach that uses the structural information from the protein data base (PDB) for developing heterotypic peptide materials via self-assembly.
结构生物学的进展揭示了蛋白质结构中肽序列之间存在许多非共价相互作用，但在开发肽材料方面，这类信息的研究还较少。在这里，我们报告了由炎症小体结构揭示的两个结合基序形成的异型肽水凝胶。具体而言，将自组装基序连接到炎症小体的 ASCPYD 纤维中的带正电荷或带负电荷的肽序列上，可得到相应肽的溶液。将带相反电荷和互补肽的肽添加到相应的肽溶液中，会产生异型水凝胶。流变学测量表明，互补肽的比例会影响所得水凝胶的粘弹性。圆二色性表明，互补肽的加入会导致静电相互作用，从而调节自组装。透射电子显微镜揭示了互补肽的比例控制着异型肽组装体的形态。这项工作说明了一种合理的、仿生的方法，该方法利用来自蛋白质数据库 (PDB) 的结构信息，通过自组装来开发异型肽材料。
