title: Structural study of MCPIP1 N-terminal conserved domain reveals a PIN-like RNase.
abstract: MCP-1-induced protein 1 (MCPIP1) plays an important role in the downregulation of the LPS-induced immune response by acting as an RNase targeting IL-6 and IL-12b mRNAs. A conserved domain located in the N-terminal part of MCPIP1 is thought to be responsible for its RNase activity, but its catalytic mechanism is not well understood due to the lack of an atomic resolution structure. We determined the 3D crystal structure of this MCPIP1 N-terminal conserved RNase domain at a resolution of 2.0 Å. The overall structure of MCPIP1 N-terminal conserved domain shares high structural homology with PilT N-terminal domain. We show that the RNase catalytic center is composed of several acidic residues, verifying their importance by site-specific mutagenesis. A positively charged arm close to the catalytic center may act as an RNA substrate-binding site, since exchange of critical positively charged residues on this arm with alanine partially abolish the RNase activity of MCPIP1 in vivo. Our structure of the MCPIP1 N-terminal conserved domain reveals the details of the catalytic center and provides a greater understanding of the RNA degradation mechanism.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.forename: Yao
authors.initials: Y
authors.lastname: Sun
authors.forename: Xiangxi
authors.initials: X
authors.lastname: Wang
authors.forename: Yihui
authors.initials: Y
authors.lastname: Xu
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
authors.forename: Guangxia
authors.initials: G
authors.lastname: Gao
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
mesh_terms: D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D017124:Conserved Sequence; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012260:Ribonucleases / Q000737:chemistry* / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D015850:Interleukin-6; D014157:Transcription Factors; D012313:RNA; D012260:Ribonucleases; C510646:ZC3H12A protein, human; C541320:Zc3h12a protein, mouse