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-Structure paper
タイトル | Structural insights into TSC complex assembly and GAP activity on Rheb. |
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ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 339, Year 2021 |
掲載日 | 2021年1月12日 |
著者 | Huirong Yang / Zishuo Yu / Xizi Chen / Jiabei Li / Ningning Li / Jiaxuan Cheng / Ning Gao / Hai-Xin Yuan / Dan Ye / Kun-Liang Guan / Yanhui Xu / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:33436626 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.56 - 4.4 Å |
構造データ | EMDB-30708, PDB-7dl2: EMDB-30709: EMDB-30710: EMDB-30711: |
由来 |
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キーワード | GENE REGULATION / TSC complex / Regulator of cell growth / GTPase-activating protein / Elongated arch-shaped fold |