Toma-Fukai Sachiko, Kim Jun-Dal, Park Kyung-Eui, Kuwabara Naoyuki, Shimizu Nobutaka, Krayukhina Elena, Uchiyama Susumu, Fukamizu Akiyoshi, Shimizu Toshiyuki
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Ibaraki 305-8577, Japan.
J Mol Biol. 2016 Mar 27;428(6):1197-1208. doi: 10.1016/j.jmb.2016.02.007. Epub 2016 Feb 11.
Protein arginine methyltransferase 8 (PRMT8) is unique among PRMTs, as it is specifically expressed in brain and localized to the plasma membrane via N-terminal myristoylation. Here, we describe the crystal structure of human PRMT8 (hPRMT8) at 3.0-Å resolution. The crystal structure of hPRMT8 exhibited a novel helical assembly. Biochemical, biophysical and mutagenesis experiments demonstrated that hPRMT8 forms an octamer in solution. This octameric structure is necessary for proper localization to the plasma membrane and efficient methyltransferase activity. The helical assembly might be a relevant quaternary form for hPRMT1, which is the predominant PRMT in mammalian cells and most closely related to hPRMT8.
蛋白质精氨酸甲基转移酶8（PRMT8）在蛋白质精氨酸甲基转移酶中独具特色，因为它在大脑中特异性表达，并通过N端肉豆蔻酰化定位于质膜。在此，我们描述了人PRMT8（hPRMT8）在3.0埃分辨率下的晶体结构。hPRMT8的晶体结构呈现出一种新型的螺旋组装。生化、生物物理和诱变实验表明，hPRMT8在溶液中形成八聚体。这种八聚体结构对于正确定位于质膜和高效的甲基转移酶活性是必需的。这种螺旋组装可能是hPRMT1的一种相关四级结构形式，hPRMT1是哺乳动物细胞中主要的蛋白质精氨酸甲基转移酶，与hPRMT8关系最为密切。
