6BT2

Structure of the human Nocturnin catalytic domain with bound sulfate anion

6BT2 の概要

• エントリーDOI: 10.2210/pdb6bt2/pdb
• 関連するPDBエントリー: 6BT1
• 分子名称: Nocturnin, MAGNESIUM ION, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: hydrolase, eep superfamily, rna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 71651.96

構造登録者

Abshire, E.T.,Chasseur, J.,Del Rizzo, P.,Trievel, R. (登録日: 2017-12-04, 公開日: 2018-05-16, 最終更新日: 2024-04-03)

主引用文献

T Abshire, E.,Chasseur, J.,Bohn, J.A.,Del Rizzo, P.A.,Freddolino, P.L.,Goldstrohm, A.C.,Trievel, R.C.
The structure of human Nocturnin reveals a conserved ribonuclease domain that represses target transcript translation and abundance in cells.
Nucleic Acids Res., 46:6257-6270, 2018

PubMed Abstract: The circadian protein Nocturnin (NOCT) belongs to the exonuclease, endonuclease and phosphatase superfamily and is most similar to the CCR4-class of deadenylases that degrade the poly-adenosine tails of mRNAs. NOCT-deficient mice are resistant to high-fat diet induced weight gain, and exhibit dysregulation of bone formation. However, the mechanisms by which NOCT regulates these processes remain to be determined. Here, we describe a pair of high-resolution crystal structures of the human NOCT catalytic domain. The active site of NOCT is highly conserved with other exoribonucleases, and when directed to a transcript in cells, NOCT can reduce translation and abundance of that mRNA in a manner dependent on key active site residues. In contrast to the related deadenylase CNOT6L, purified recombinant NOCT lacks in vitro ribonuclease activity, suggesting that unidentified factors are necessary for enzymatic activity. We also find the ability of NOCT to repress reporter mRNAs in cells depends upon the 3' end of the mRNA, as reporters terminating with a 3' MALAT1 structure cannot be repressed by NOCT. Together, these data demonstrate that NOCT is an exoribonuclease that can degrade mRNAs to inhibit protein expression, suggesting a molecular mechanism for its regulatory role in lipid metabolism and bone development.

PubMed: 29860338
DOI: 10.1093/nar/gky412

実験手法

X-RAY DIFFRACTION (2.411 Å)