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题目：Molecular study of Rag GTPase-dependent amino acid sensing
演讲人：Kuang Shen, Ph.D.
Postdocoral Fellow,
Whitehead Insititute for Biomedical Research,
MIT, HHMI
时间：2019年5月7日13:00-14:00
地点：吕志和楼B106
摘要:
mTORC1 is a major regulator of cell behavior that responds to environmental stimuli to promote cell growth. One of the major stimuli that mTORC1 responds to is the amino acids in the lysosome, which stimulate mTORC1 activity through a signaling cascade that ultimately converges to the heterodimeric Rag GTPases. The Rag GTPase dimer directly contacts mTORC1 to recruit it to the lysosomal surface, where its activator Rheb resides. Despite its significance, the molecular mechanism of this unique GTPase dimer remains elusive. We developed biochemical and biophysical tools to study the Rag GTPases. First, we built a unified kinetic framework to study the behavior of the Rag GTPases and clarified the molecular function of Ragulator and SLC38A9, two positive regulators of mTORC1 pathway. Second, we used cryo-EM to resolve the structure of GATOR1, a major negative regulator of the Rag GTPases, as well as the structure of GATOR1-Rag GTPases complex. These analyses provided details on how signals are passed through the Rag GTPases to mTORC1, and opened up a new realm of biophysical studies on amino acid sensing.
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