Molecular complementarity and structural heterogeneity within co-assembled peptide β-sheet nanofibers
Molecular complementarity and structural heterogeneity within co-assembled peptide β-sheet nanofibers
复制标题
共组装肽β片纳米纤维内的分子互补性和结构异质性
DOI：
10.1039/c9nr08725g
复制
发表时间：
2020
期刊：
影响因子：
6.7
通讯作者：
Paravastu, Anant K.
中科院分区：
文献类型：
--
作者：
Wong, Kong M.;Wang, Yiming;Seroski, Dillon T.;Larkin, Grant E.;Mehta, Anil K.;Hudalla, Gregory A.;Hall, Carol K.;Paravastu, Anant K.
自组装肽作为一种功能性生物材料在医学和生物技术领域的应用越来越受到人们的关注。最近，利用由定位成赋予共组装行为的带电氨基酸组成的肽的互补对的β折叠肽设计已经扩大了肽聚集体结构的组合。这些电荷互补肽共组装体的结构表征受到限制。因此，不知道互补肽在分子水平上如何组织。通过固体核磁共振测量和不连续分子动力学模拟相结合，我们研究了King-Webb肽纳米纤维的分子组织。通过计算模拟和13 C-13 C偶极偶联观察到，KW+和KW−肽共组装成接近化学计量的双组分β折叠结构。如先前通过傅里叶变换红外光谱测量所建议的，大多数β链与β折叠内的反平行最近邻对齐。然而，令人惊讶的是，相当大比例的β-链邻居是平行的。虽然电荷互补肽以前被假定为组织在一个理想的（AB）n模式，偶极重耦合测量同位素稀释的样品中揭示了不可忽略的量的自相关（AA和BB）对。此外，计算机模拟预测这些不同的结构可以共存于同一个晶体中。我们的研究结果突出了在分子水平上的电荷互补肽系统的结构紊乱与共组装肽设计的影响。
Self-assembling peptides have garnered an increasing amount of interest as a functional biomaterial for medical and biotechnological applications. Recently, β-sheet peptide designs utilizing complementary pairs of peptides composed of charged amino acids positioned to impart co-assembly behavior have expanded the portfolio of peptide aggregate structures. Structural characterization of these charge-complementary peptide co-assemblies has been limited. Thus, it is not known how the complementary peptides organize on the molecular level. Through a combination of solid-state NMR measurements and discontinuous molecular dynamics simulations, we investigate the molecular organization of King–Webb peptide nanofibers. KW+ and KW− peptides co-assemble into near stoichiometric two-component β-sheet structures as observed by computational simulations and 13C–13C dipolar couplings. A majority of β-strands are aligned with antiparallel nearest neighbors within the β-sheet as previously suggested by Fourier transform infrared spectroscopy measurements. Surprisingly, however, a significant proportion of β-strand neighbors are parallel. While charge-complementary peptides were previously assumed to organize in an ideal (AB)n pattern, dipolar recoupling measurements on isotopically diluted nanofiber samples reveal a non-negligible amount of self-associated (AA and BB) pairs. Furthermore, computational simulations predict these different structures can coexist within the same nanofiber. Our results highlight structural disorder at the molecular level in a charge-complementary peptide system with implications on co-assembling peptide designs.