STRUCTURAL BIOLOGY Architecture of human mTOR complex 1

被引：264

作者：

Aylett, Christopher H. S. ^{[1
]}

Sauer, Evelyn ^{[2
]}

Imseng, Stefan ^{[2
]}

Boehringer, Daniel ^{[1
]}

Hall, Michael N. ^{[2
]}

Ban, Nenad ^{[1
]}

Maier, Timm ^{[2
]}

机构：

[1] ETH, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland

[2] Univ Basel, Biozentrum, Basel, Switzerland

来源：

SCIENCE | 2016年 / 351卷 / 6268期

基金：

瑞士国家科学基金会; 欧洲研究理事会;

关键词：

PEPTIDYL-PROLYL ISOMERASE; CELL-GROWTH; IMMUNOSUPPRESSANT FK506; MAMMALIAN PROTEIN; BINDING PARTNER; DIRECT TARGET; RAG GTPASES; TOS MOTIF; RAPAMYCIN; RAPTOR;

D O I：

10.1126/science.aaa3870

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Target of rapamycin (TOR), a conserved protein kinase and central controller of cell growth, functions in two structurally and functionally distinct complexes: TORC1 and TORC2. Dysregulation of mammalian TOR (mTOR) signaling is implicated in pathologies that include diabetes, cancer, and neurodegeneration. We resolved the architecture of human mTORC1 (mTOR with subunits Raptor and mLST8) bound to FK506 binding protein (FKBP)-rapamycin, by combining cryo-electron microscopy at 5.9 angstrom resolution with crystallographic studies of Chaetomium thermophilum Raptor at 4.3 angstromresolution. The structure explains how FKBP-rapamycin and architectural elements of mTORC1 limit access to the recessed active site. Consistent with a role in substrate recognition and delivery, the conserved amino-terminal domain of Raptor is juxtaposed to the kinase active site.

引用

页码：48 / 52

页数：5

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