Histatin-5（一种内在无序的唾液肽）中的特定金属蛋白相互作用和抗菌活性。,Scientific Reports

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Histatin-5（一种内在无序的唾液肽）中的特定金属蛋白相互作用和抗菌活性。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-11-21 , DOI: 10.1038/s41598-019-52676-7
Tyler G McCaslin _{1,

2} , Cynthia V Pagba _{1,

2} , Jiby Yohannan _{1,

2} , Bridgette A Barry _{1,

2}

Affiliation

Histatin-5（Hst-5）是一种抗菌，唾液蛋白，参与宿主防御系统。已经提出Hst-5结合功能相关的锌和铜，但是由于其在水溶液中的无序构象而在结构研究中提出了挑战。在这里，我们使用圆二色性（CD）和紫外共振拉曼（UVRR）光谱来定义水溶液中的Metallo-Hst-5相互作用。相对于在不存在锌的情况下观察到的带，含锌的Hst-5样品表现出移动的拉曼谱带。根据与模型化合物和一系列设计的，与锌结合的β发夹的比较，Hst-5 UVRR光谱的变化归因于咪唑侧链对锌的配位作用。锌的添加还通过静电相互作用改变了酪氨酸芳香环的UVRR带。铜的添加没有这些作用。使用了序列变体H18A / H19A。与Hst-5相比，此突变体的抗真菌活性较低。添加锌对该突变体的热稳定性仅有很小的影响。有趣的是，锌和铜的添加都以诊断金属配位的方式移动了组氨酸UVRR带。用K13E / R22G突变体获得的结果与用野生型获得的结果相似。这些实验表明H18和H19有助于锌结合位点。在H18A / H19A突变体中，铜/锌结合位点的特异性丧失。实验暗示特定的锌结合在Hst-5的抗菌活性中很重要。锌的添加对该突变体的热稳定性只有很小的影响。有趣的是，锌和铜的添加都以诊断金属配位的方式移动了组氨酸UVRR带。用K13E / R22G突变体获得的结果与用野生型获得的结果相似。这些实验表明H18和H19有助于锌结合位点。在H18A / H19A突变体中，铜/锌结合位点的特异性丧失。实验暗示特定的锌结合对Hst-5的抗菌活性很重要。锌的添加对该突变体的热稳定性只有很小的影响。有趣的是，锌和铜的添加都以诊断金属配位的方式移动了组氨酸UVRR带。用K13E / R22G突变体获得的结果与用野生型获得的结果相似。这些实验表明H18和H19有助于锌结合位点。在H18A / H19A突变体中，铜/锌结合位点的特异性丧失。实验暗示特定的锌结合在Hst-5的抗菌活性中很重要。这些实验表明H18和H19有助于锌结合位点。在H18A / H19A突变体中，铜/锌结合位点的特异性丧失。实验暗示特定的锌结合在Hst-5的抗菌活性中很重要。这些实验表明H18和H19有助于锌结合位点。在H18A / H19A突变体中，铜/锌结合位点的特异性丧失。实验暗示特定的锌结合在Hst-5的抗菌活性中很重要。

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Specific metallo-protein interactions and antimicrobial activity in Histatin-5, an intrinsically disordered salivary peptide.

Histatin-5 (Hst-5) is an antimicrobial, salivary protein that is involved in the host defense system. Hst-5 has been proposed to bind functionally relevant zinc and copper but presents challenges in structural studies due to its disordered conformation in aqueous solution. Here, we used circular dichroism (CD) and UV resonance Raman (UVRR) spectroscopy to define metallo-Hst-5 interactions in aqueous solution. A zinc-containing Hst-5 sample exhibits shifted Raman bands, relative to bands observed in the absence of zinc. Based on comparison to model compounds and to a family of designed, zinc-binding beta hairpins, the alterations in the Hst-5 UVRR spectrum are attributed to zinc coordination by imidazole side chains. Zinc addition also shifted a tyrosine aromatic ring UVRR band through an electrostatic interaction. Copper addition did not have these effects. A sequence variant, H18A/H19A, was employed; this mutant has less potent antifungal activity, when compared to Hst-5. Zinc addition had only a small effect on the thermal stability of this mutant. Interestingly, both zinc and copper addition shifted histidine UVRR bands in a manner diagnostic for metal coordination. Results obtained with a K13E/R22G mutant were similar to those obtained with wildtype. These experiments show that H18 and H19 contribute to a zinc binding site. In the H18A/H19A mutant the specificity of the copper/zinc binding sites is lost. The experiments implicate specific zinc binding to be important in the antimicrobial activity of Hst-5.

更新日期：2019-11-21

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