Site-Specific Analysis of Gas-Phase Hydrogen/Deuterium Exchange of Peptides and Proteins by Electron Transfer Dissociation

被引:57
作者
Rand, Kasper D. [1 ]
Pringle, Steven D. [2 ]
Morris, Michael [2 ]
Brown, Jeffery M. [2 ]
机构
[1] Univ Copenhagen, Dept Pharmaceut & Analyt Chem, Copenhagen, Denmark
[2] Micromass UK Ltd, Waters MS Technol Ctr, Manchester M23 9LZ, Lancs, England
关键词
CYTOCHROME-C IONS; HYDROGEN-DEUTERIUM EXCHANGE; SINGLE-RESIDUE RESOLUTION; MASS-SPECTROMETRY; CAPTURE DISSOCIATION; H/D EXCHANGE; UBIQUITIN IONS; STRUCTURAL TRANSITIONS; PROTONATED PEPTIDES; VAPOR-PHASE;
D O I
10.1021/ac202918j
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
To interpret the wealth of information contained in the hydrogen/deuterium exchange (HDX) behavior of peptides and proteins in the gas-phase, analytical tools are needed to resolve the HDX of individual exchanging sites. Here we show that ETD can be combined with fast gas-phase HDX in ND3 gas and used to monitor the exchange of side-chain hydrogens of individual residues in both small peptide ions and larger protein ions a few milliseconds after electrospray. By employing consecutive traveling wave ion guides in a mass spectrometer, peptide and protein ions were labeled on-the-fly (0.1-10 ms) in ND3 gas and subsequently fragmented by ETD. Fragment ions were separated using ion mobility and mass analysis enabled the determination of the gas-phase deuterium uptake of individual side-chain sites in a range of model peptides of different size and sequence as well as two proteins; cytochrome C and ubiquitin. Gas-phase HDX-ETD experiments on ubiquitin ions ionized from both denaturing and native solution conditions suggest that residue-specific HDX of side-chain hydrogens is sensitive to secondary and tertiary structural features occurring in both near-native and unfolded gas-phase conformers present shortly after electrospray. The described approach for online gas-phase HDX and ETD paves the way for making mass spectrometry techniques based on gas-phase HDX more applicable in bioanalytical research.
引用
收藏
页码:1931 / 1940
页数:10
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