Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain

被引：92

作者：

Croll, Tristan I. ^{[1
]}

Smith, Brian J. ^{[2
]}

Margetts, Mai B. ^{[3
]}

Whittaker, Jonathan ^{[4
]}

Weiss, Michael A. ^{[4
,5
,6
]}

Ward, Colin W. ^{[3
]}

Lawrence, Michael C. ^{[3
,7
]}

机构：

[1] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4059, Australia

[2] La Trobe Univ, La Trobe Inst Mol Sci, Melbourne, Vic 3086, Australia

[3] Walter & Eliza Hall Inst Med Res, Struct Biol Div, Parkville, Vic 3052, Australia

[4] Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA

[5] Case Western Reserve Univ, Dept Physiol, Cleveland, OH 44106 USA

[6] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA

[7] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia

来源：

STRUCTURE | 2016年 / 24卷 / 03期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

MOLECULAR-DYNAMICS; MUTANT ALLELES; BINDING-SITES; RESISTANCE; REFINEMENT; ACTIVATION; MODEL; GENE;

D O I：

10.1016/j.str.2015.12.014

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：

Insulin receptor (IR) signaling is critical to controlling nutrient uptake and metabolism. However, only a low-resolution (3.8 angstrom) structure currently exists for the IR ectodomain, with some segments ill-defined or unmodeled due to disorder. Here, we revise this structure using new diffraction data to 3.3 angstrom resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding.

引用

页码：469 / 476

页数：8

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