6BT1

Structure of the human Nocturnin catalytic domain

Summary for 6BT1

• Entry DOI: 10.2210/pdb6bt1/pdb
• Descriptor: Nocturnin, MAGNESIUM ION (3 entities in total)
• Functional Keywords: hydrolase, eep superfamily, rna binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 35729.92

Authors

Abshire, E.T.,Chasseur, J.,Del Rizzo, P.,Trievel, R. (deposition date: 2017-12-04, release date: 2018-05-16, Last modification date: 2024-03-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.48 Å)