From the Units of Molecular Immunology.
J Biol Chem. 2013 Dec 6;288(49):35093-103. doi: 10.1074/jbc.M113.511949. Epub 2013 Oct 15.
Although lysine methylation is classically known to regulate histone function, its role in modulating antiviral restriction factor activity remains uncharacterized. Interferon-induced transmembrane protein 3 (IFITM3) was found monomethylated on its lysine 88 residue (IFITM3-K88me1) to reduce its antiviral activity, mediated by the lysine methyltransferase SET7. Vesicular stomatitis virus and influenza A virus infection increased IFITM3-K88me1 levels by promoting the interaction between IFITM3 and SET7, suggesting that this pathway could be hijacked to support infection; conversely, IFN-α reduced IFITM3-K88me1 levels. These findings may have important implications in the design of therapeutics targeting protein methylation against infectious diseases.
尽管赖氨酸甲基化被经典地认为可以调节组蛋白功能，但它在调节抗病毒限制因子活性方面的作用仍未被阐明。干扰素诱导的跨膜蛋白 3（IFITM3）在其赖氨酸 88 残基上被单甲基化（IFITM3-K88me1），以降低其抗病毒活性，这一过程由赖氨酸甲基转移酶 SET7 介导。水疱性口炎病毒和甲型流感病毒感染通过促进 IFITM3 和 SET7 之间的相互作用增加了 IFITM3-K88me1 水平，提示该途径可能被劫持以支持感染；相反，IFN-α 降低了 IFITM3-K88me1 水平。这些发现对于针对传染病的靶向蛋白质甲基化的治疗药物的设计可能具有重要意义。
