Combining native and 'omics' mass spectrometry to identify endogenous ligands bound to membrane proteins

被引：127

作者：

Gault, Joseph ^{[1
]}

Liko, Idlir ^{[1
,2
]}

Landreh, Michael ^{[3
]}

Shutin, Denis ^{[1
]}

Bolla, Jani Reddy ^{[1
]}

Jefferies, Damien ^{[4
]}

Agasid, Mark ^{[1
]}

Yen, Hsin-Yung ^{[2
]}

Ladds, Marcus J. G. W. ^{[3
]}

Lane, David P. ^{[3
]}

Khalid, Syma ^{[4
]}

Mullen, Christopher ^{[5
]}

Remes, Philip M. ^{[5
]}

Huguet, Romain ^{[5
]}

McAlister, Graeme ^{[5
]}

Goodwin, Michael ^{[5
]}

Viner, Rosa ^{[5
]}

Syka, John E. P. ^{[5
]}

Robinson, Carol V. ^{[1
]}

机构：

[1] Univ Oxford, Dept Chem, Oxford, England

[2] OMass Therapeut, Oxford, England

[3] Karolinska Inst, Biomedicum, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden

[4] Univ Southampton, Sch Chem, Southampton, Hants, England

[5] Thermo Fisher Sci, San Jose, CA USA

来源：

NATURE METHODS | 2020年 / 17卷 / 05期

基金：

英国医学研究理事会; 英国惠康基金; 英国工程与自然科学研究理事会; 欧洲研究理事会;

关键词：

CRYSTAL-STRUCTURES; 18; KDA; TSPO; VALIDATION; COMPLEXES; BINDING;

D O I：

10.1038/s41592-020-0821-0

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

'Nativeomics' enables identification of ligands bound to membrane proteins through detection of intact protein-ligand assemblies followed by dissociation and identification of individual ligands within the same mass spectrometry experiment. Ligands bound to protein assemblies provide critical information for function, yet are often difficult to capture and define. Here we develop a top-down method, 'nativeomics', unifying 'omics' (lipidomics, proteomics, metabolomics) analysis with native mass spectrometry to identify ligands bound to membrane protein assemblies. By maintaining the link between proteins and ligands, we define the lipidome/metabolome in contact with membrane porins and a mitochondrial translocator to discover potential regulators of protein function.

引用

页码：505 / +

页数：17

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