1I7E

C-Terminal Domain Of Mouse Brain Tubby Protein bound to Phosphatidylinositol 4,5-bis-phosphate

Summary for 1I7E

• Entry DOI: 10.2210/pdb1i7e/pdb
• Related: 1C8Z
• Descriptor: TUBBY PROTEIN, L-ALPHA-GLYCEROPHOSPHO-D-MYO-INOSITOL-4,5-BIS-PHOSPHATE (3 entities in total)
• Functional Keywords: tubby filled-barrel beta-barrel filled-beta-roll 12-stranded-beta-barrel helix-filled-barrel obesity blindness deafness phosphoinositide phosphatidylinositol, signaling protein
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm: P50586
• Total number of polymer chains: 1
• Total formula weight: 30489.35

Authors

Santagata, S.,Boggon, T.J.,Baird, C.L.,Shan, W.S.,Shapiro, L. (deposition date: 2001-03-08, release date: 2001-06-27, Last modification date: 2023-08-09)

Primary citation

Santagata, S.,Boggon, T.J.,Baird, C.L.,Gomez, C.A.,Zhao, J.,Shan, W.S.,Myszka, D.G.,Shapiro, L.
G-protein signaling through tubby proteins.
Science, 292:2041-2050, 2001

PubMed Abstract: Dysfunction of the tubby protein results in maturity-onset obesity in mice. Tubby has been implicated as a transcription regulator, but details of the molecular mechanism underlying its function remain unclear. Here we show that tubby functions in signal transduction from heterotrimeric GTP-binding protein (G protein)-coupled receptors. Tubby localizes to the plasma membrane by binding phosphatidylinositol 4,5-bisphosphate through its carboxyl terminal "tubby domain." X-ray crystallography reveals the atomic-level basis of this interaction and implicates tubby domains as phosphorylated-phosphatidyl- inositol binding factors. Receptor-mediated activation of G protein alphaq (Galphaq) releases tubby from the plasma membrane through the action of phospholipase C-beta, triggering translocation of tubby to the cell nucleus. The localization of tubby-like protein 3 (TULP3) is similarly regulated. These data suggest that tubby proteins function as membrane-bound transcription regulators that translocate to the nucleus in response to phosphoinositide hydrolysis, providing a direct link between G-protein signaling and the regulation of gene expression.

PubMed: 11375483
DOI: 10.1126/science.1061233

Experimental method

X-RAY DIFFRACTION (1.95 Å)