Ganoderma microsporum immunomodulatory protein
| Ganoderma microsporum immunomodulatory protein | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | GMI | ||||||
| Pfam | PF09259 | ||||||
| InterPro | IPR015339 | ||||||
| |||||||
| https://pubchem.ncbi.nlm.nih.gov/substance/461501955 | |||||||
Ganoderma microsporum immunomodulatory protein or GMI is a protein discovered from the mushroom species Ganoderma microsporum.[1][2] GMI is a pure protein composed of 111 amino acids and exists in nature as a tetramer.[3]
Discovery
GMI is found in the mycelium of Ganoderma microsporum. During the life cycle of G. microsporum, GMI acts as an important signaling factor in the transition from the fungi's mycelium phase to the fruiting body phase. However, the levels of GMI found in both the mycelium and fruiting body are very low.
In 2005, researchers utilized genetic and bio-engineering methods to obtain purified GMI, and proved that the protein is structurally similar to LZ-8, the first fungal immunomodulatory protein discovered in 1989. The name GMI is derived from the fact that when cultured with immune cells, GMI was found to not only increase the cells' hormone production, but also induce higher levels of cellular activity.[4]
Immunomodulatory functions
GMI has been observed to exhibit a variety of antitumor properties, including inhibition of cancer cell proliferation, tumor suppression, and enhancement of autophagy and apoptosis, all of which are driven mainly through induction of epidermal growth factor receptor (EGFR) degradation[5]. Its ability to modulate immune responses has also provoked an interest in studying its possible antiviral properties and therapeutic potential. Recently, GMI was observed to interfere with SARS-CoV-2 infection by blocking viral attachment and membrane fusion through binding the viral spike protein as well as the host ACE2 receptor[6]. GMI also inhibits SARS-CoV-2 pro-inflammatory mediators, which are key drivers of hyper-inflammatory responses associated with severe COVID-19 and can contribute to severe tissue injury and multi-organ damage. Beyond coronaviruses, GMI has shown inhibitory effects against several herpesviruses, including Epstein-Barr virus (EBV) and Herpes simplex virus 1 (HSV-1). GMI inhibits herpesvirus infection by disrupting membrane fusion during viral entry, primarily through binding to the widely conserved glycoprotein gB[7]. These observations suggest that GMI could have broad-spectrum antiviral properties, although all current observations derive from in vitro studies and require confirmation in vivo.
References
- ^ Teo WH, Lo JF, Fan YN, Huang CY, Huang TF (2020). "Ganoderma microsporum immunomodulatory protein, GMI, promotes C2C12 myoblast differentiation in vitro via upregulation of Tid1 and STAT3 acetylation". PLOS ONE. 15 (12) e0244791. Bibcode:2020PLoSO..1544791T. doi:10.1371/journal.pone.0244791. PMC 7774968. PMID 33382817.
- ^ Huang SY, Chien CC, Hseu RS, Huang VY, Chiang SY, Huang CJ, et al. (June 2018). "Ganoderma microsporum immunomodulatory protein induces apoptosis and potentiates mitomycin C-induced apoptosis in urinary bladder urothelial carcinoma cells". Journal of Cellular Biochemistry. 119 (6): 4592–4606. doi:10.1002/jcb.26616. PMID 29240252. S2CID 206028088.
- ^ Wu MY, Hsu MF, Huang CS, Fu HY, Wang AH, Hseu RS, Huang CT, Yang CS (November 2007). A 2.0 Å Structure of the Fungal Immunomodulatory Protein GMI from Ganoderma microsporum. The 2nd Asia-Oceania Forum for Synchrotron Radiation Research.
- ^ US 7601808, Lin TL, "Immunomodulatory protein cloned from ganoderma microsporum", issued 13 Oct. 2009, assigned to MycoMagic Biotechnology Co., Ltd.
- ^ Hua, Wei-Jyun; Yeh, Hsin; Lin, Zhi-Hu; Tseng, Ai-Jung; Huang, Li-Chen; Qiu, Wei-Lun; Tu, Tsung-Hsi; Wang, Ding-Han; Hsu, Wei-Hung; Hwang, Wei-Lun; Lin, Tung-Yi (December 2023). "Ganoderma microsporum immunomodulatory protein as an extracellular epidermal growth factor receptor (EGFR) degrader for suppressing EGFR-positive lung cancer cells". Cancer Letters. 578 216458. doi:10.1016/j.canlet.2023.216458.
- ^ Ho, Ha Phan Thanh; Vo, Di Ngoc Kha; Lin, Tung-Yi; Hung, Jo-Ning; Chiu, Ya-Hui; Tsai, Ming-Han (November 2022). "Ganoderma microsporum immunomodulatory protein acts as a multifunctional broad-spectrum antiviral against SARS-CoV-2 by interfering virus binding to the host cells and spike-mediated cell fusion". Biomedicine & Pharmacotherapy. 155 113766. doi:10.1016/j.biopha.2022.113766. PMC 9515347. PMID 36271550.
- ^ Vo, Di Ngoc Kha; Ho, Ha Phan Thanh; Wu, Li-Syuan; Chen, Yi-Yun; Trinh, Hang Thi Viet; Lin, Tung-Yi; Lim, Yat-Yuen; Tsai, Keng-Chang; Tsai, Ming-Han (May 2025). "Broad-spectrum antiviral activity of Ganoderma microsporum immunomodulatory protein: Targeting glycoprotein gB to inhibit EBV and HSV-1 infections via viral fusion blockage". International Journal of Biological Macromolecules. 307 142179. doi:10.1016/j.ijbiomac.2025.142179.