{Reference Type}: Journal Article
{Title}: Regulation of mTOR by phosphatidic acid.
{Author}: Frias MA;Hatipoglu A;Foster DA;
{Journal}: Trends Endocrinol Metab
{Volume}: 34
{Issue}: 3
{Year}: 03 2023
{Factor}: 10.586
{DOI}: 10.1016/j.tem.2023.01.004
{Abstract}: mTORC1, the mammalian target of rapamycin complex 1, is a key regulator of cellular physiology. The lipid metabolite phosphatidic acid (PA) binds to and activates mTORC1 in response to nutrients and growth factors. We review structural findings and propose a model for PA activation of mTORC1. PA binds to a highly conserved sequence in the α4 helix of the FK506 binding protein 12 (FKBP12)/rapamycin-binding (FRB) domain of mTOR. It is proposed that PA binding to two adjacent positively charged amino acids breaks and shortens the C-terminal region of helix α4. This has profound consequences for both substrate binding and the catalytic activity of mTORC1.