4Q9V

Crystal structure of TIPE3

Summary for 4Q9V

• Entry DOI: 10.2210/pdb4q9v/pdb
• Related: 3F4M
• Descriptor: Tumor necrosis factor alpha-induced protein 8-like protein 3, CHLORIDE ION, SULFATE ION, ... (4 entities in total)
• Functional Keywords: helix, lipid transfer protein, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 44224.06

Authors

Wu, J.,Zhang, X.,Chen, Y.H.,Shi, Y. (deposition date: 2014-05-02, release date: 2014-10-22, Last modification date: 2023-11-08)

Primary citation

Fayngerts, S.A.,Wu, J.,Oxley, C.L.,Liu, X.,Vourekas, A.,Cathopoulis, T.,Wang, Z.,Cui, J.,Liu, S.,Sun, H.,Lemmon, M.A.,Zhang, L.,Shi, Y.,Chen, Y.H.
TIPE3 Is the Transfer Protein of Lipid Second Messengers that Promote Cancer.
Cancer Cell, 26:465-478, 2014

PubMed Abstract: More than half of human cancers have aberrantly upregulated phosphoinositide signals; yet how phospholipid signals are controlled during tumorigenesis is not fully understood. We report here that TIPE3 (TNFAIP8L3) is the transfer protein of phosphoinositide second messengers that promote cancer. High-resolution crystal structure of TIPE3 shows a large hydrophobic cavity that is occupied by a phospholipid-like molecule. TIPE3 preferentially captures and shuttles two lipid second messengers, i.e., phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate, and increases their levels in the plasma membrane. Notably, human cancers have markedly upregulated TIPE3 expression. Knocking out TIPE3 diminishes tumorigenesis, whereas enforced TIPE3 expression enhances it in vivo. Thus, the function and metabolism of phosphoinositide second messengers are controlled by a specific transfer protein during tumorigenesis.

PubMed: 25242044
DOI: 10.1016/j.ccr.2014.07.025

Experimental method

X-RAY DIFFRACTION (2.3 Å)