5JXD

Crystal structure of murine Tnfaip8 C165S mutant

Summary for 5JXD

• Entry DOI: 10.2210/pdb5jxd/pdb
• Descriptor: Tumor necrosis factor alpha-induced protein 8, [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate (3 entities in total)
• Functional Keywords: tnfaip8, oxi-a, phosphatidylethanolamine, immune system
• Biological source: Mus musculus (Mouse)
• Cellular location: Cytoplasm : Q921Z5
• Total number of polymer chains: 1
• Total formula weight: 23699.43

Authors

Park, J.,Kim, M.S.,Lee, D.,Shin, D.H. (deposition date: 2016-05-13, release date: 2017-06-28, Last modification date: 2023-11-08)

Primary citation

Kim, J.S.,Park, J.,Kim, M.S.,Ha, J.Y.,Jang, Y.W.,Shin, D.H.,Son, J.H.
The Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action of insulin
Sci Rep, 7:6248-6248, 2017

PubMed Abstract: Defective hepatic autophagy is observed in obesity and diabetes, whereas autophagy is inhibited by insulin in hepatocytes. Insulin-induced anti-autophagy is mediated by non-canonical Gαi3 signaling via an unknown mechanism. Previously, we identified the anti-autophagic activity of Tnfaip8 via activation of mammalian target of rapamycin (mTOR) in the nervous system. Here, we demonstrate that insulin temporally induces Tnfaip8, which mediates the anti-autophagic action of insulin through formation of a novel ternary complex including Tnfaip8, phosphatidylethanolamine (PE) and Gαi3. Specifically, an X-ray crystallographic study of Tnfaip8 from Mus musculus (mTnfaip8) at 2.03 Å together with LC-MS analyses reveals PE in the hydrophobic cavity. However, an mTnfaip8 mutant lacking PE does not interact with Gαi3, indicating that the PE component is critical for the anti-autophagic action of mTnfaip8 via interaction with Gαi3. Therefore, the mTnfaip8-PE complex may act as an essential upstream effector via ternary complex formation most likely with active Gαi3 during insulin-induced anti-autophagy.

PubMed: 28740220
DOI: 10.1038/s41598-017-06576-3

Experimental method

X-RAY DIFFRACTION (2.029 Å)