title: Novel helical assembly in arginine methyltransferase 8.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Toma-Fukai
authors.affiliation: Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Ibaraki 305-8577, Japan.
authors.forename: Jun-Dal
authors.initials: JD
authors.lastname: Kim
authors.affiliation: Graduate School of Life & Environmental Science, University of Tsukuba, 1-1-1 Tennoudai, Ibaraki 305-8577, Japan.
authors.forename: Kyung-Eui
authors.initials: KE
authors.lastname: Park
authors.affiliation: Structural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba, Ibaraki 305-0801, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kuwabara
authors.affiliation: Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba, Ibaraki 305-0801, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Shimizu
authors.affiliation: Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan; U-Medico, Corp., 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Elena
authors.initials: E
authors.lastname: Krayukhina
authors.affiliation: Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Uchiyama
authors.affiliation: Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Ibaraki 305-8577, Japan; Graduate School of Life & Environmental Science, University of Tsukuba, 1-1-1 Tennoudai, Ibaraki 305-8577, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: shimizu@mol.f.u-tokyo.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D018360:Crystallography, X-Ray; D004252:DNA Mutational Analysis; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; C505447:PRMT8 protein, human; D011484:Protein-Arginine N-Methyltransferases
keywords: FRET; PRMT; X-ray crystallography; oligomerization; small angle X-ray scattering