%0 Journal Article
%T Regulation of mTOR by phosphatidic acid.
%A Frias MA
%A Hatipoglu A
%A Foster DA
%J Trends Endocrinol Metab
%V 34
%N 3
%D 03 2023
%M 36732094
%F 10.586
%R 10.1016/j.tem.2023.01.004
%X 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.