Novel helical assembly in arginine methyltransferase 8. Issue 6 (27th March 2016)

• Record Type: Journal Article
• Authors: Toma-Fukai, Sachiko; Kim, Jun-Dal; Park, Kyung-Eui; Kuwabara, Naoyuki; Shimizu, Nobutaka; Krayukhina, Elena; Uchiyama, Susumu; Fukamizu, Akiyoshi; Shimizu, Toshiyuki
• Is Part Of: Journal of molecular biology. Volume 428:Issue 6(2016:Mar. 27)
• Page Start: 1197
• Page End: 1208
• Publication Date: 2016-03-27
• Subjects: PRMT8 Protein arginine methyltransferase 8 -- SEC size exclusion chromatography -- SAXS small angle X-ray scattering -- MALS multi-angle light scattering -- AUC analytical ultracentrifugation -- SAH S-adenosyl homocysteine -- BiFC bimolecular-fluorescence complementation -- Sc Saccharomyces cerevisiae -- PBS phosphate-buffered saline -- CBB Coomassie Brilliant Blue -- HEK human embryonic kidney; PRMT -- oligomerization -- X-ray crystallography -- small angle X-ray scattering -- FRET; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2016.02.007
• Languages: English
• ISSNs: 0022-2836

Abstract

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 ( h PRMT8) at 3.0-Å resolution. The crystal structure of h PRMT8 exhibited a novel helical assembly. Biochemical, biophysical and mutagenesis experiments demonstrated that h PRMT8 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 h PRMT1, which is the predominant PRMT in mammalian cells and most closely related to h PRMT8. Graphical abstract: Highlights: PRMT8 is a type I protein arginine methyltransferase. The crystal structure of PRMT8 exhibits a novel helical assembly. The oligomerization is necessary for proper function of this enzyme. The oligomerization state is required for cellular localization.