Global analysis of protein structural changes in complex proteomes

被引：281

作者：

Feng, Yuehan ^{[1
]}

De Franceschi, Giorgia ^{[1
,2
]}

Kahraman, Abdullah ^{[1
]}

Soste, Martin ^{[1
]}

Melnik, Andre ^{[1
]}

Boersema, Paul J. ^{[1
]}

de laureto, Patrizia Polverino ^{[2
]}

Nikolaev, Yaroslav ^{[3
]}

Oliveira, Ana Paula ^{[4
]}

Picotti, Paola ^{[1
]}

机构：

[1] ETH, Inst Biochem, Dept Biol, Zurich, Switzerland

[2] Univ Padua, CRIBI Biotechnol Ctr, Padua, Italy

[3] ETH, Inst Mol Biol & Biophys, Dept Biol, Zurich, Switzerland

[4] ETH, Inst Mol Syst Biol, Dept Biol, Zurich, Switzerland

来源：

NATURE BIOTECHNOLOGY | 2014年 / 32卷 / 10期

关键词：

CONFORMATIONAL-CHANGES; SACCHAROMYCES-CEREVISIAE; LIMITED PROTEOLYSIS; MASS-SPECTROMETRY; ALLOSTERY; CLEAVAGE; ENZYME; METABOLISM; EFFICIENCY; ASSEMBLIES;

D O I：

10.1038/nbt.2999

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Changes in protein conformation can affect protein function, but methods to probe these structural changes on a global scale in cells have been lacking. To enable large-scale analyses of protein conformational changes directly in their biological matrices, we present a method that couples limited proteolysis with a targeted proteomics workflow. Using our method, we assessed the structural features of more than 1,000 yeast proteins simultaneously and detected altered conformations for similar to 300 proteins upon a change of nutrients. We find that some branches of carbon metabolism are transcriptionally regulated whereas others are regulated by enzyme conformational changes. We detect structural changes in aggregation-prone proteins and show the functional relevance of one of these proteins to the metabolic switch. This approach enables probing of both subtle and pronounced structural changes of proteins on a large scale.

引用

页码：1036 / +

页数：13

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[11] MSstats: an R package for statistical analysis of quantitative mass spectrometry-based proteomic experiments [J].