Zn(2+) ions selectively induce antimicrobial salivary peptide histatin-5 to fuse negatively charged vesicles. Identification and characterization of a zinc-binding motif present in the functional domain.
Zn(2+) ions selectively induce antimicrobial salivary peptide histatin-5 to fuse negatively charged vesicles. Identification and characterization of a zinc-binding motif present in the functional domain.
复制标题
Zn(2) 离子选择性诱导抗菌唾液肽 Histatin-5 融合带负电的囊泡。
作者：
S. Melino;S. Rufini;M. Sette;R. Morero;A. Grottesi;M. Paci;R. Petruzzelli
唾液抗菌肽组蛋白-5能够聚集和融合带负电荷的小单层囊泡，并且这种融合活性由锌离子的存在选择性地诱导。圆二色性光谱表明，组胺素-5，在带负电荷的囊泡和锌离子的存在下，经历了构象变化，导致稳定的α-螺旋二级结构。我们将锌离子的特异性作用归因于一个共有序列HEXXH的存在，HEXXH位于组胺素-5的C-末端功能域，组胺素-5是许多蛋白质中公认的锌结合基序。二维质子核磁共振波谱的histatin-5在三氟乙醇/水的混合物（膜模拟环境）已进行和结果分析的距离几何和约束的分子动力学模拟。我们的研究结果表明，肽链，包括锌结合的共识序列对应的残基15-19，是在螺旋构象。组胺素-5中的各个氨基酸的化学位移与最近报道的其他溶剂中的化学位移的比较表明，三氟乙醇/水具有介于水和二甲基亚砜之间的结构化能力。这种抗菌肽的作用机制进行了讨论的基础上，其结构特点，特别注意锌结合基序。
The salivary antimicrobial peptide histatin-5 is able to aggregate and fuse negatively charged small unilamellar vesicles, and this fusogenic activity is selectively induced by the presence of zinc ions. Circular dichroism spectroscopy shows that histatin-5, in the presence of negatively charged vesicles and zinc ions, undergoes a conformational change leading to the stabilization of an alpha-helical secondary structure. We attribute the specific action of the zinc ions to the presence of a consensus sequence, HEXXH, located in the C-terminal functional domain of histatin-5, a recognized zinc-binding motif in many proteins. Two-dimensional proton NMR spectroscopy of histatin-5 in a trifluoroethanol/water mixture (a membrane mimetic environment) has been performed and the results analyzed by means of distance geometry and restrained molecular dynamics simulations. Our results reveal that the peptide chain, including the Zn-binding consensus sequence corresponding to residues 15-19, is in a helicoidal conformation. Comparison of the chemical shifts of the individual amino acids in histatin-5 with those recently reported in other solvents indicates that trifluoroethanol/water has a structuring capability somewhere between water and dimethyl sulfoxide. The mechanism of action of this antimicrobial peptide is discussed on the basis of its structural characteristics with particular attention to the Zn-binding motif.