Journal
INTERNATIONAL JOURNAL OF MEDICINAL MUSHROOMS
Volume 20, Issue 6, Pages 537-548Publisher
BEGELL HOUSE INC
DOI: 10.1615/IntJMedMushrooms.2018026264
Keywords
dimerization; electrostatic interaction; fungal immunomodulatory proteins (FIPs); Ganoderma lucidum; LZ-8; medicinal mushrooms; protein-protein docking
Funding
- Shanghai Municipal Agricultural Commission, Shanghai, P.R. China [1-14]
- Shanghai Engineering Research Center of Edible Fungi [16DZ2281300]
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Ling zhi-8 (LZ-8) is the first fungal immunomodulatory protein (HP) 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 volyacca, 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.
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