7a0m | pdb_00007a0m

TSC1 N-terminal domain

spinqualitylabelsall models 7a0m, resolution 2.32Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7a0m is a 4 chain structure with sequence from Cbs 144.50. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4 NonStd Res: MSE Gene: CTHT_0033260 (CBS 144.50) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The TSC complex is a critical negative regulator of the small GTPase Rheb and mTORC1 in cellular stress signaling. The TSC2 subunit contains a catalytic GTPase activating protein domain and interacts with multiple regulators, while the precise function of TSC1 is unknown. Here we provide a structural characterization of TSC1 and define three domains: a C-terminal coiled-coil that interacts with TSC2, a central helical domain that mediates TSC1 oligomerization, and an N-terminal HEAT repeat domain that interacts with membrane phosphatidylinositol phosphates (PIPs). TSC1 architecture, oligomerization, and membrane binding are conserved in fungi and humans. We show that lysosomal recruitment of the TSC complex and subsequent inactivation of mTORC1 upon starvation depend on the marker lipid PI3,5P2, demonstrating a role for lysosomal PIPs in regulating TSC complex and mTORC1 activity via TSC1. Our study thus identifies a vital role of TSC1 in TSC complex function and mTORC1 signaling. TSC1 binding to lysosomal PIPs is required for TSC complex translocation and mTORC1 regulation.,Fitzian K, Bruckner A, Brohee L, Zech R, Antoni C, Kiontke S, Gasper R, Linard Matos AL, Beel S, Wilhelm S, Gerke V, Ungermann C, Nellist M, Raunser S, Demetriades C, Oeckinghaus A, Kummel D Mol Cell. 2021 Apr 30. pii: S1097-2765(21)00324-5. doi:, 10.1016/j.molcel.2021.04.019. PMID:33974911 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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