Cell type-specific nuclear pores: a case in point for context-dependent stoichiometry of molecular machines

被引：237

作者：

Ori, Alessandro ^{[1
]}

Banterle, Niccolo ^{[1
]}

Iskar, Murat ^{[1
]}

Andres-Pons, Amparo ^{[1
]}

Escher, Claudia ^{[2
]}

Bui, Huy Khanh ^{[1
]}

Sparks, Lenore ^{[1
]}

Solis-Mezarino, Victor ^{[1
]}

Rinner, Oliver ^{[2
]}

Bork, Peer ^{[1
]}

Lemke, Edward A. ^{[1
]}

Beck, Martin ^{[1
]}

机构：

[1] European Mol Biol Lab, Struct & Computat Biol Unit, D-69117 Heidelberg, Germany

[2] Biognosys AG, Schlieren, Switzerland

来源：

MOLECULAR SYSTEMS BIOLOGY | 2013年 / 9卷

基金：

瑞士国家科学基金会; 欧洲研究理事会;

关键词：

fluorophore counting; nucleoporin; protein complex-based analysis; super-resolution microscopy; targeted proteomics; CHROMATIN REMODELING COMPLEX; GENE-EXPRESSION; NUP107-160; COMPLEX; NUCLEOPORIN; ARCHITECTURE; PROTEINS; ENVELOPE; BINDING; NUP214; MODULE;

D O I：

10.1038/msb.2013.4

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：

To understand the structure and function of large molecular machines, accurate knowledge of their stoichiometry is essential. In this study, we developed an integrated targeted proteomics and super-resolution microscopy approach to determine the absolute stoichiometry of the human nuclear pore complex (NPC), possibly the largest eukaryotic protein complex. We show that the human NPC has a previously unanticipated stoichiometry that varies across cancer cell types, tissues and in disease. Using large-scale proteomics, we provide evidence that more than one third of the known, well-defined nuclear protein complexes display a similar cell type-specific variation of their subunit stoichiometry. Our data point to compositional rearrangement as a widespread mechanism for adapting the functions of molecular machines toward cell type-specific constraints and context-dependent needs, and highlight the need of deeper investigation of such structural variants. Molecular Systems Biology 9: 648; published online 19 March 2013; doi: 10.1038/msb.2013.4

引用

页数：11

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