Powis, Katie Zhang, Tianlong Panchaud, Nicolas Wang, Rong De Virgilio, Claudio Ding, Jianping 2015-07-24 The target of rapamycin complex 1 (TORC1) integrates various hormonal and nutrient signals to regulate cell growth, proliferation, and differentiation. Amino acid-dependent activation of TORC1 is mediated via the yeast EGO complex (EGOC) consisting of Gtr1, Gtr2, Ego1, and Ego3. Here, we identify the previously uncharacterized Ycr075w-a/Ego2 protein as an additional EGOC component that is required for the integrity and localization of the heterodimeric Gtr1-Gtr2 GTPases, equivalent to mammalian Rag GTPases. We also report the crystal structure of the Ego1-Ego2-Ego3 ternary complex (EGO-TC) at 2.4 Å resolution, in which Ego2 and Ego3 form a heterodimer flanked along one side by Ego1. Structural data also reveal the structural conservation of protein components between the yeast EGO-TC and the human Ragulator, which acts as a GEF for Rag GTPases. Interestingly, however, artificial tethering of Gtr1-Gtr2 to the vacuolar membrane is sufficient to activate TORC1 in response to amino acids even in the absence of the EGO-TC. Our structural and functional data therefore support a model in which the EGO-TC acts as a scaffold for Rag GTPases in TORC1 signaling. application/pdf https://folia.unifr.ch/global/documents/304539 https://folia.unifr.ch/documents/304539/files/dev_cse.pdf https://folia.unifr.ch/documents/304539/files/dev_cse_sm.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1038/cr.2015.86 info:eu-repo/semantics/openAccess License undefined Cell Research. - 2015, vol. 25, no. 9, p. 1043–1059 Crystal structure EGO complex Rag GTPase TORC1 signaling growth control info:eu-repo/classification/udc/57 Crystal structure of the Ego1-Ego2-Ego3 complex and its role in promoting Rag GTPase-dependent TORC1 signaling http://purl.org/coar/resource_type/c_6501