Mollusk hemocyanins, among the largest known proteins, are used as immunostimulants in biomedical and clinical applications. The hemocyanin of the Chilean gastropod (CCH) exhibits unique properties, which makes it safe and effective for human immunotherapy, as observed in animal models of bladder cancer and melanoma, and dendritical cell vaccine trials. Despite its potential, the structure and amino acid sequence of CCH remain unknown. This study reports two sequence fragments of CCH, representing three complete functional units (FUs). We also determined the high-resolution (1.5 Å) X-ray crystal structure of an “FU-g type” from the CCHB subunit. This structure enables in-depth analysis of chemical interactions at the copper-binding center and unveils an unusual, truncated N-glycosylation pattern. These features are linked to eliciting more robust immunological responses in animals, offering insights into CCH’s enhanced immunostimulatory properties and opening new avenues for its potential applications in biomedical research and therapies.

中文翻译：

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从免疫原性软体动物血蓝蛋白中了解功能单元的结构


软体动物血蓝蛋白是已知最大的蛋白质之一，在生物医学和临床应用中用作免疫刺激剂。智利腹足动物 (CCH) 的血蓝蛋白具有独特的特性，这使得它对于人类免疫治疗安全有效，正如在膀胱癌和黑色素瘤动物模型以及树突状细胞疫苗试验中所观察到的那样。尽管具有潜力，CCH 的结构和氨基酸序列仍然未知。这项研究报告了 CCH 的两个序列片段，代表三个完整的功能单元 (FU)。我们还确定了 CCHB 亚基“FU-g 型”的高分辨率 (1.5 Å) X 射线晶体结构。这种结构能够深入分析铜结合中心的化学相互作用，并揭示一种不寻常的、截短的 N-糖基化模式。这些特征与在动物体内引发更强大的免疫反应有关，为了解 CCH 增强的免疫刺激特性提供了见解，并为其在生物医学研究和治疗中的潜在应用开辟了新途径。