Novel helical assembly in arginine methyltransferase 8

Sachiko Toma-Fukai; Jun-Dal Kim; Kyung-Eui Park; Naoyuki Kuwabara; Nobutaka Shimizu; Elena Krayukhina; Susumu Uchiyama; Akiyoshi Fukamizu; Toshiyuki Shimizu

doi:10.1016/j.jmb.2016.02.007

Novel helical assembly in arginine methyltransferase 8

J Mol Biol. 2016 Mar 27;428(6):1197-1208. doi: 10.1016/j.jmb.2016.02.007. Epub 2016 Feb 11.

Authors

Sachiko Toma-Fukai¹, Jun-Dal Kim², Kyung-Eui Park³, Naoyuki Kuwabara⁴, Nobutaka Shimizu⁵, Elena Krayukhina⁶, Susumu Uchiyama⁷, Akiyoshi Fukamizu⁸, Toshiyuki Shimizu⁹

Affiliations

¹ Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
² Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Ibaraki 305-8577, Japan.
³ Graduate School of Life & Environmental Science, University of Tsukuba, 1-1-1 Tennoudai, Ibaraki 305-8577, Japan.
⁴ 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.
⁵ Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba, Ibaraki 305-0801, Japan.
⁶ 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.
⁷ Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
⁸ 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.
⁹ 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.

PMID: 26876602
DOI: 10.1016/j.jmb.2016.02.007

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.

Keywords: FRET; PRMT; X-ray crystallography; oligomerization; small angle X-ray scattering.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Crystallography, X-Ray
DNA Mutational Analysis
Humans
Membrane Proteins / chemistry*
Membrane Proteins / metabolism*
Protein Multimerization
Protein Structure, Secondary
Protein-Arginine N-Methyltransferases / chemistry*
Protein-Arginine N-Methyltransferases / metabolism*

Substances

Membrane Proteins
PRMT8 protein, human
Protein-Arginine N-Methyltransferases