Boyle Aimee L, Rabe Martin, Crone Niek S A, Rhys Guto G, Soler Nicolas, Voskamp Patrick, Pannu Navraj S, Kros Alexander
Leiden Institute of Chemistry , Leiden University , Einsteinweg 55 , 2333 CC Leiden , The Netherlands . Email:
Max-Planck-Institut für Eisenforschung GmbH , Max-Planck-Straße 1 , 40237 Düsseldorf , Germany.
Chem Sci. 2019 Jun 20;10(31):7456-7465. doi: 10.1039/c9sc01165j. eCollection 2019 Aug 21.
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 α-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.
设计能响应金属离子而折叠和组装的肽，考验着我们对肽折叠与金属结合如何相互影响的理解。在此，将组氨酸残基引入卷曲螺旋三聚体的疏水核心，生成一种在添加金属离子后会自组装的肽。所得的肽HisAD在无金属时无结构，与Cu(ii)和Ni(ii)络合时选择性折叠形成α螺旋结构，而与Co(ii)或Zn(ii)络合时则不然。使用圆二色性（CD）光谱、分析超速离心（AUC）、核磁共振（NMR）光谱和X射线晶体学相结合的方法，对HisAD的结构和金属结合能力进行了探究。这些结果表明，该肽呈三聚体形式，且如设计的那样，以1∶1的比例与参与金属配位的组氨酸残基结合Cu(ii)和Ni(ii)。HisAD-Cu(ii)复合物的X射线晶体结构揭示三聚体HisAD肽配位三个Cu(ii)离子；这是此类结构的首个实例。此外，HisAD对过渡金属离子表现出前所未有的区分能力，其基础可能与形成的肽-金属复合物的稳定性有关。
