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Mistletoe lectin I (ML-I), also known as Viscumin, is a type II ribosome-inactivating protein (RIP) derived from the European mistletoe plant, Viscum album (UniProt P06750). It is a heterodimeric glycoprotein consisting of an A-chain with N-glycosidase activity and a B-chain that functions as a lectin. The B-chain specifically binds to cell-surface galactoside-containing glycoconjugates, such as those containing terminal galactose or N-acetylgalactosamine residues, which facilitates the internalization of the lectin via receptor-mediated endocytosis (National Cancer Institute, 2023). Once inside the cytosol, the A-chain inhibits protein synthesis by depurinating the 28S ribosomal RNA of the 60S ribosomal subunit, leading to cell cycle arrest and apoptosis (PubChem CID 16212654). ML-I also exhibits significant immunomodulatory effects, including the activation of natural killer (NK) cells, macrophages, and the induction of cytokine release, such as interleukin-1 and tumor necrosis factor-alpha (Büssing et al., 2011). Clinically, mistletoe extracts containing ML-I are utilized as complementary therapies in oncology to improve patient quality of life and reduce the adverse effects of conventional cancer treatments.
The B-chain of the lectin binds to cell-surface galactoside-containing glycoconjugates, facilitating receptor-mediated endocytosis. Once internalized, the A-chain acts as an N-glycosidase that depurinates the 28S ribosomal RNA, leading to the irreversible inhibition of protein synthesis and subsequent apoptosis.
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