PDF(Pubmed)
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.
摘要：
mTORC1是哺乳动物雷帕霉素复合物1的靶标，是细胞生理学的关键调节剂。脂质代谢产物磷脂酸(PA)结合并激活mTORC1以响应营养物和生长因子。我们回顾了结构发现，并提出了PA激活mTORC1的模型。PA结合mTOR的FK506结合蛋白12(FKBP12)/雷帕霉素结合(FRB)结构域的α4螺旋中的高度保守序列。提出了PA与两个相邻的带正电荷的氨基酸的结合会破坏并缩短螺旋α4的C末端区域。这对底物结合和mTORC1的催化活性都有深远的影响。
