Architecture and activation of phosphatidylinositol 3-kinase related kinases

被引：44

作者：

Imseng, Stefan ^{[1
]}

Aylett, Christopher H. S. ^{[2
]}

Maier, Timm ^{[1
]}

机构：

[1] Univ Basel, Biozentrum, Basel, Switzerland

[2] Dept Med, Sect Struct Biol, Imperial Coll Rd, London SW7 2BB, England

来源：

CURRENT OPINION IN STRUCTURAL BIOLOGY | 2018年 / 49卷

基金：

英国惠康基金;

关键词：

STRAND BREAK REPAIR; CRYO-EM STRUCTURE; PEPTIDYL-PROLYL ISOMERASE; PIK-RELATED KINASES; DNA-PK HOLOENZYME; MTOR COMPLEX 1; IMMUNOSUPPRESSANT FK506; BINDING PARTNER; PROTEIN-KINASE; GROWTH-CONTROL;

D O I：

10.1016/j.sbi.2018.03.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The phosphatidylinositol 3-kinase related protein kinases (PIKKs) are key to the regulation of a variety of eukaryotic cellular processes including DNA repair and growth regulation. While these massive proteins had long resisted structural analysis, recent advances in electron cryo-microscopy have now facilitated structural analysis of the major examples of PIKKs, including mTOR, DNA-PK, ATM, ATR and TRAPP/Tra1. In these PIKKs, the carboxy-terminal kinase domains and their proximal regions are structurally conserved. The structural organization of their extensive amino-terminal repeat regions, however, as well as their oligomeric organization and their interactions with accessory proteins, differ markedly amongst PIKKs. This architectural divergence provides the structural basis for the complex regulatory roles and functional diversity of PIKKs.

引用

页码：177 / 189

页数：13

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[21] SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity [J].