Abstract：
Eukaryotic cells coordinate available nutrients with their growth through the mechanistic target of rapamycin complex 1 (mTORC1) pathway, in which numerous evolutionarily conserved protein complexes survey and transmit nutrient inputs toward mTORC1. mTORC1 integrates these inputs and activates downstream anabolic or catabolic programs that are in tune with cellular needs, effectively maintaining metabolic homeostasis. The GAP activity toward Rags-1 (GATOR1) protein complex is a critical negative regulator of the mTORC1 pathway and, in the absence of amino acid inputs, is activated to turn off mTORC1 signaling. GATOR1-mediated inhibition of mTORC1 signaling is tightly regulated by an ensemble of protein complexes that antagonize or promote its activity in response to the cellular nutrient environment. Structural, biochemical, and biophysical studies of the GATOR1 complex and its interactors have advanced our understanding of how it regulates cellular metabolism when amino acids are limited. Here, we review the current research with a focus on GATOR1 structure, its enzymatic mechanism, and the growing group of proteins that regulate its activity. Finally, we discuss the implication of GATOR1 dysregulation in physiology and human diseases.
摘要：
真核细胞通过雷帕霉素复合物1（mTORC1）途径的机制靶标与它们的生长协调可用营养素，其中许多进化上保守的蛋白质复合物调查并将营养输入传递给mTORC1。mTORC1集成这些输入和激活下游的合成代谢或分解代谢程序，与细胞的需求，有效维持代谢稳态。对Rags-1（GATOR1）蛋白复合物的GAP活性是mTORC1途径的关键负调节因子，在没有氨基酸输入的情况下，被激活以关闭mTORC1信令。GATOR1介导的mTORC1信号传导的抑制受到一组蛋白质复合物的严格调节，这些蛋白质复合物拮抗或促进其响应于细胞营养环境的活性。结构,生物化学，和生物物理研究的GATOR1复合体和它的相互作用，提高了我们的理解，它是如何调节细胞代谢时，氨基酸是有限的。这里,我们回顾了当前的研究，重点是GATOR1结构，其酶促机理，以及越来越多的调节其活性的蛋白质。最后,我们讨论了GATOR1失调在生理和人类疾病中的意义。
