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Information × Registration Number 0125U002747, R & D request Title Structural and functional basis of the participation of human leucyl-tRNA synthetase in leucine-dependent mTORC1 signaling pathways Head Tukalo Mykhailo А., Доктор біологічних наук Registration Date 19-06-2025 Organization Institute of Molecular Biology and Genetics of NAS of Ukraine popup.description1 The aim of this project is to study the structural and functional basis of the participation of human leucyl-tRNA synthetase (LeuRS) in leucine-dependent signaling pathways of the mechanistic Target of Rapamycin complex 1 (mTORC1). Through computer modeling and biochemical experiments, we will conduct a detailed test of the hypothesis of the participation of LeuRS as a leucine sensor in amino acid-dependent mTORC1 signaling pathways. Also, the sensitivity of leucine sensors to non-proteinogenic leucine analogues (norvaline, norleucine, and homocysteine) will be studied by biochemical methods. To study the structural basis of the conformational changes that occur when LeuRS switches from tRNA to RagD binding and the mechanism of its promotion of the conversion of RagD-GTP to RagD-GDP, methods that allow working in solution will be used: cryo-EM, fluorescence spectroscopy, molecular docking and molecular dynamics. The implementation of the tasks set in the project will deepen the understanding of the role of leucine-dependent mTORС1 pathways in the regulation and coordination of cellular functions, as well as their role in tumorigenesis from the point of view of targeted antitumor therapy, which is the key to the development of new therapeutic drugs and approaches in the treatment of patients. popup.nrat_date 2025-06-19 Close