7DL2

Cryo-EM structure of human TSC complex

7DL2 の概要

• エントリーDOI: 10.2210/pdb7dl2/pdb
• EMDBエントリー: 30708 30709 30710 30711
• 分子名称: Hamartin, Isoform 7 of Tuberin, TBC1 domain family member 7, ... (4 entities in total)
• 機能のキーワード: tsc complex, regulator of cell growth, gtpase-activating protein, elongated arch-shaped fold, gene regulation
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 689396.78

構造登録者

Yang, H.,Yu, Z.,Chen, X.,Li, J.,Li, N.,Cheng, J.,Gao, N.,Yuan, H.,Ye, D.,Guan, K.,Xu, Y. (登録日: 2020-11-25, 公開日: 2020-12-16, 最終更新日: 2024-03-27)

主引用文献

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

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: 33436626
DOI: 10.1038/s41467-020-20522-4

実験手法

ELECTRON MICROSCOPY (4.4 Å)