Selective coordination of three transition metal ions within a coiled-coil peptide scaffold
Selective coordination of three transition metal ions within a coiled-coil peptide scaffold
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DOI：
10.1039/c9sc01165j
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发表时间：
2019-08-21
期刊：
影响因子：
8.4
通讯作者：
Kros, Alexander
中科院分区：
文献类型：
--
作者：
Boyle, Aimee L.;Rabe, Martin;Kros, Alexander
设计折叠和组装响应金属离子的肽测试我们对肽折叠和金属结合如何相互影响的理解。在这里，组氨酸残基被引入到一个线圈三聚体的疏水核心，产生一个肽，在添加金属离子后自组装。所得到的HisAD肽在没有金属的情况下是非结构化的，并且在与Cu（ii）和Ni（ii）而不是Co（ii）或Zn（ii）络合时选择性地折叠形成α -螺旋结构。利用圆二色性（CD）光谱、分析超离心（AUC）、核磁共振（NMR）光谱和x射线晶体学的组合来探测HisAD的结构和金属结合能力。这些结果表明，该肽是三聚体，并与铜（ii）和镍（ii）以1:1的比例结合，其组氨酸残基参与金属配位，如设计的那样。HisAD-Cu（ii）配合物的x射线晶体结构揭示了三聚体HisAD肽配位三个Cu（ii）离子；这是这种结构的第一个例子。此外，HisAD在过渡金属离子之间表现出前所未有的区别，其基础可能与形成的肽-金属配合物的稳定性有关。
Designing peptides that fold and assemble in response to metal ions tests our understanding of how peptide folding and metal binding influence one another. Here, histidine residues are introduced into the hydrophobic core of a coiled-coil trimer, generating a peptide that self-assembles upon the addition of metal ions. HisAD, the resulting peptide, is unstructured in the absence of metal and folds selectively to form an alpha-helical construct upon complexation with Cu(ii) and Ni(ii) but not Co(ii) or Zn(ii). The structure, and metal-binding ability, of HisAD is probed using a combination of circular dichroism (CD) spectroscopy, analytical ultracentrifugation (AUC), nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography. These show the peptide is trimeric and binds to both Cu(ii) and Ni(ii) in a 1 : 1 ratio with the histidine residues involved in the metal coordination, as designed. The X-ray crystal structure of the HisAD-Cu(ii) complex reveals the trimeric HisAD peptide coordinates three Cu(ii) ions; this is the first example of such a structure. Additionally, HisAD demonstrates an unprecedented discrimination between transition metal ions, the basis of which is likely to be related to the stability of the peptide-metal complexes formed.