Bao Da-Peng, Bai Rui, Gao Ying-Nv, Wu Ying-Ying, Wang Ying
Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, Key Laboratory of Agricultural Genetics and Breeding, Ministry of Agriculture, National Engineering Research Center for Edible Fungi, National R&D Center for Edible Fungi Processing, Key Laboratory of Agricultural Genetics and Breeding of Shanghai, Shanghai, People's Republic of China.
College of Food Science, Shanghai Ocean University, Shanghai, People's Republic of China.
Int J Med Mushrooms. 2018;20(6):537-548. doi: 10.1615/IntJMedMushrooms.2018026264.
Ling zhi-8 (LZ-8) is the first fungal immunomodulatory protein (FIP) isolated from the lingzhi or reishi medicinal mushroom, Ganoderma lucidum. LZ-8 effectively induces interleukin 2 expression and secretion by forming a stable homodimer, and it is regarded as a good candidate to become a new therapeutic agent and/or functional food supplement. However, the molecular mechanism by which LZ-8 dimerization influences the regulation of interleukin 2 is not clear. In this study we performed structure-based multiple alignment of LZ-8 and an FIP from Volvariella volvacea, compared the electrostatic potential of their protein surfaces, and developed a model summarizing the unique electrostatic interaction in LZ-8 dimerization. In addition, further electrostatic potential and virtual amino acid mutation analyses suggested that L10, W12, and D45 are the key amino acid residues responsible for the protein's high immunomodulatory activity. These findings may provide useful insights into the design and construction of a new FIP mutant for use in treating and preventing autoimmune diseases.
灵芝-8（LZ-8）是从灵芝或赤芝药用蘑菇中分离出的首个真菌免疫调节蛋白（FIP）。LZ-8通过形成稳定的同二聚体有效诱导白细胞介素2的表达和分泌，被视为成为新型治疗药物和/或功能性食品补充剂的良好候选物。然而，LZ-8二聚化影响白细胞介素2调节的分子机制尚不清楚。在本研究中，我们对LZ-8和草菇中的一种FIP进行了基于结构的多重比对，比较了它们蛋白质表面的静电势，并建立了一个总结LZ-8二聚化中独特静电相互作用的模型。此外，进一步的静电势和虚拟氨基酸突变分析表明，L10、W12和D45是负责该蛋白质高免疫调节活性的关键氨基酸残基。这些发现可能为设计和构建用于治疗和预防自身免疫性疾病的新型FIP突变体提供有用的见解。
