Structure of the Schizosaccharomyces Pombe Gtr-Lam Complex Reveals Evolutionary Divergence of Mtorc1-Dependent Amino Acid Sensing.

mTORC1 is a protein kinase complex that controls cellular growth in response to nutrient availability. Amino acid signals are transmitted toward mTORC1 via the Rag/Gtr GTPases and their upstream regulators. An important regulator is LAMTOR, which localizes Rag/Gtr on the lysosomal/vacuole membrane. In human cells, LAMTOR consists of five subunits, but in yeast, only three or four. Currently, it is not known how vari-ation of the subunit stoichiometry may affect its structural organization and biochemical properties. Here, we report a 3.1 A-resolution structural model of the Gtr-Lam complex in Schizosaccharomyces pombe. We found that SpGtr shares conserved architecture as HsRag, but the intersubunit communication that coordi-nates nucleotide loading on the two subunits differs. In contrast, SpLam contains distinctive structural fea-tures, but its GTP-specific GEF activity toward SpGtr is evolutionarily conserved. Our results revealed unique of the of the mTORC1