Structural basis for the regulation of enzymatic activity of Regnase-1 by domain-domain interactions

Mariko Yokogawa, Takashi Tsushima, Nobuo N. Noda, Hiroyuki Kumeta, Yoshiaki Enokizono, Kazuo Yamashita, Daron M. Standley, Osamu Takeuchi, Shizuo Akira, Fuyuhiko Inagaki

研究成果: Article査読

31 被引用数 (Scopus)

抄録

Regnase-1 is an RNase that directly cleaves mRNAs of inflammatory genes such as IL-6 and IL-12p40, and negatively regulates cellular inflammatory responses. Here, we report the structures of four domains of Regnase-1 from Mus musculus - the N-terminal domain (NTD), PilT N-terminus like (PIN) domain, zinc finger (ZF) domain and C-terminal domain (CTD). The PIN domain harbors the RNase catalytic center; however, it is insufficient for enzymatic activity. We found that the NTD associates with the PIN domain and significantly enhances its RNase activity. The PIN domain forms a head-to-tail oligomer and the dimer interface overlaps with the NTD binding site. Interestingly, mutations blocking PIN oligomerization had no RNase activity, indicating that both oligomerization and NTD binding are crucial for RNase activity in vitro. These results suggest that Regnase-1 RNase activity is tightly controlled by both intramolecular (NTD-PIN) and intermolecular (PIN-PIN) interactions.

本文言語English
論文番号22324
ジャーナルScientific reports
6
DOI
出版ステータスPublished - 2016 3 1
外部発表はい

ASJC Scopus subject areas

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