The mammalian target of rapamycin,mTOR,forms various protein-protein complexes to regulate cell growth in response to the nutrient and energy status of the cell.Recently,the first crystal structure of large HEAT repea...The mammalian target of rapamycin,mTOR,forms various protein-protein complexes to regulate cell growth in response to the nutrient and energy status of the cell.Recently,the first crystal structure of large HEAT repeat protein mTOR revealed that the FAT domain interacts with the kinase domain through electrostatic effects and hydrophobic interactions.Based on the structure,the previous researches on how FAT domain regulates mTOR activity are reviewed.DEPTOR is currently known as an endogenous mTOR inhibitor,which may interact with mTOR FAT domain to suppress mTOR activity in vivo.The possible interactions of DEPTOR with the mTOR FAT domain are analyzed,too.In addition,the inhibition mechanism of DEPTOR may be similar to members of HEAT-involved RanGTP complex family,providing new mechanistic insights into mTOR kinase regulation.展开更多
基金supported by the National Natural Science Foundation of China(21133003,21273023)Specialized Research Fund for the Doctoral Program of Higher Education(20110003120013)
文摘The mammalian target of rapamycin,mTOR,forms various protein-protein complexes to regulate cell growth in response to the nutrient and energy status of the cell.Recently,the first crystal structure of large HEAT repeat protein mTOR revealed that the FAT domain interacts with the kinase domain through electrostatic effects and hydrophobic interactions.Based on the structure,the previous researches on how FAT domain regulates mTOR activity are reviewed.DEPTOR is currently known as an endogenous mTOR inhibitor,which may interact with mTOR FAT domain to suppress mTOR activity in vivo.The possible interactions of DEPTOR with the mTOR FAT domain are analyzed,too.In addition,the inhibition mechanism of DEPTOR may be similar to members of HEAT-involved RanGTP complex family,providing new mechanistic insights into mTOR kinase regulation.
