7DL2
Cryo-EM structure of human TSC complex
Summary for 7DL2
| Entry DOI | 10.2210/pdb7dl2/pdb |
| EMDB information | 30708 30709 30710 30711 |
| Descriptor | Hamartin, Isoform 7 of Tuberin, TBC1 domain family member 7, ... (4 entities in total) |
| Functional Keywords | tsc complex, regulator of cell growth, gtpase-activating protein, elongated arch-shaped fold, gene regulation |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 689396.78 |
| Authors | |
| Primary citation | Yang, H.,Yu, Z.,Chen, X.,Li, J.,Li, N.,Cheng, J.,Gao, N.,Yuan, H.X.,Ye, D.,Guan, K.L.,Xu, Y. Structural insights into TSC complex assembly and GAP activity on Rheb. Nat Commun, 12:339-339, 2021 Cited by PubMed Abstract: Tuberous sclerosis complex (TSC) integrates upstream stimuli and regulates cell growth by controlling the activity of mTORC1. TSC complex functions as a GTPase-activating protein (GAP) towards small GTPase Rheb and inhibits Rheb-mediated activation of mTORC1. Mutations in TSC genes cause tuberous sclerosis. In this study, the near-atomic resolution structure of human TSC complex reveals an arch-shaped architecture, with a 2:2:1 stoichiometry of TSC1, TSC2, and TBC1D7. This asymmetric complex consists of two interweaved TSC1 coiled-coil and one TBC1D7 that spans over the tail-to-tail TSC2 dimer. The two TSC2 GAP domains are symmetrically cradled within the core module formed by TSC2 dimerization domain and central coiled-coil of TSC1. Structural and biochemical analyses reveal TSC2 GAP-Rheb complimentary interactions and suggest a catalytic mechanism, by which an asparagine thumb (N1643) stabilizes γ-phosphate of GTP and accelerate GTP hydrolysis of Rheb. Our study reveals mechanisms of TSC complex assembly and GAP activity. PubMed: 33436626DOI: 10.1038/s41467-020-20522-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.4 Å) |
Structure validation
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