Solid-State NMR Evidence for β-Hairpin Structure within MAX8 Designer Peptide Nanofibers
Solid-State NMR Evidence for β-Hairpin Structure within MAX8 Designer Peptide Nanofibers
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DOI：
10.1016/j.bpj.2013.05.047
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发表时间：
2013-07-02
影响因子：
3.4
通讯作者：
Paravastu, Anant K.
中科院分区：
文献类型：
--
作者：
Leonard, Sarah R.;Cormier, Ashley R.;Paravastu, Anant K.
MAX8 是一种设计肽，已知会在温度、pH 和离子强度变化后进行自组装，已被证明可用于组织工程和药物输送。据推测，自组装 MAX8 纳米纤维结构由排列成反平行 β 片层的闭合 β 发夹组成。在这里，我们报告了来自固态核磁共振波谱的证据，支持纳米纤维结构中假设的 β-发夹构象的存在。具体来说，我们的 C-13-C-13 二维交换数据表明 V3 和 K17 之间的空间邻近性，而 C-13-C-13 偶极耦合测量揭示了 V3 和 V18 主链羰基之间的邻近性。此外，标记的 MAX8 纳米纤维的同位素稀释不会导致 C-13-C-13 偶极耦合的损失，表明这些耦合主要是分子内的。核磁共振谱还表明存在较小的构象，这是根据先前假设的纳米纤维物理交联和可能的纳米纤维多态性进行讨论的。
MAX8, a designer peptide known to undergo self-assembly following changes in temperature, pH, and ionic strength, has demonstrated usefulness for tissue engineering and drug delivery. It is hypothesized that the self-assembled MAX8 nanofiber structure consists of closed beta-hairpins aligned into antiparallel beta-sheets. Here, we report evidence from solid-state NMR spectroscopy that supports the presence of the hypothesized beta-hairpin conformation within the nanofiber structure. Specifically, our C-13-C-13 two-dimensional exchange data indicate spatial proximity between V3 and K17, and C-13-C-13 dipolar coupling measurements reveal proximity between the V3 and V18 backbone carbonyls. Moreover, isotopic dilution of labeled MAX8 nanofibers did not result in a loss of the C-13-C-13 dipolar couplings, showing that these couplings are primarily intramolecular. NMR spectra also indicate the existence of a minor conformation, which is discussed in terms of previously hypothesized nanofiber physical cross-linking and possible nanofiber polymorphism.