Coordination of Redox Ions within a Membrane-Binding Peptide: A Tale of Aromatic Rings
Coordination of Redox Ions within a Membrane-Binding Peptide: A Tale of Aromatic Rings
复制标题
膜结合肽内氧化还原离子的配位：芳香环的故事
DOI：
10.1021/acs.jpclett.1c00636
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Cotten, Myriam L.
中科院分区：
文献类型：
--
作者：
Fu, Riqiang;Rooney, Mary T.;Zhang, Rongfu;Cotten, Myriam L.
氨基末端铜镍结合（ATCUN）基序是一种以组氨酸结尾的三肽序列，赋予蛋白质和肽重要的功能。对膜相关蛋白和肽的ATCUN基序进行了很少的高分辨率研究，限制了我们对它们如何稳定膜中Cu 2 +/Ni 2+的理解。在这里，我们利用固态NMR来研究金属结合到piscidin-1（P1），一种以F1 F2 H3为其ATCUN基序的宿主防御肽。结合氧化还原离子，P1化学和物理破坏致病细胞膜。我们设计了13 C/15 N相关实验来检测和分配由Ni 2+结合产生和/或移动的去质子化氮。在P1-apo中占据多个化学状态，H3和相邻的H4通过仅填充τ-互变异构体来响应金属化。与远端H4相比，作为近端组氨酸的H3直接与金属配位。密度泛函理论计算反映了这种非正则排列，并指出F1/F2/H4芳环和金属之间的阳离子−π相互作用。这些结构发现与其他含ATCUN的膜肽相关，可以帮助设计用于耐药细菌，神经系统疾病和生物医学成像领域的新疗法和材料。
The amino-terminal-copper-and-nickel-binding (ATCUN) motif, a tripeptide sequence ending with a histidine, confers important functions to proteins and peptides. Few high-resolution studies have been performed on the ATCUN motifs of membrane-associated proteins and peptides, limiting our understanding of how they stabilize Cu2+/Ni2+in membranes. Here, we leverage solid-state NMR to investigate metal-binding to piscidin-1 (P1), a host-defense peptide featuring F1F2H3 as its ATCUN motif. Bound to redox ions, P1 chemically and physically damages pathogenic cell membranes. We design13C/15N correlation experiments to detect and assign the deprotonated nitrogens produced and/or shifted by Ni2+-binding. Occupying multiple chemical states in P1-apo, H3 and the neighboring H4 respond to metalation by populating only the τ-tautomer. H3, as a proximal histidine, directly coordinates the metal, compared to the distal H4. Density functional theory calculations reflect this noncanonical arrangement and point toward cation−π interactions between the F1/F2/H4 aromatic rings and metal. These structural findings, which are relevant to other ATCUN-containing membrane peptides, could help design new therapeutics and materials for use in the areas of drug-resistant bacteria, neurological disorders, and biomedical imaging.