Cross-Linking Mass Spectrometry: An Emerging Technology for Interactomics and Structural Biology

Yu, Clinton; Huang, Lan

doi:10.1021/acs.analchem.7b04431

Cited by 279 publications

(354 citation statements)

References 257 publications

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“…On the other hand, conventional photo‐crosslinkers (such as diazirines, azides, and benzophenones) target virtually all residues non‐selectively, but such nonspecific chemistry often results in highly complex crosslinked products, dramatically complicating MS data analysis. Furthermore, excessive crosslinking may artificially distort protein tertiary structures . For DNA–protein crosslinking, formaldehyde remains the primary reagent despite its short crosslink distance (approximately 2 Å) and limited reactivity with a few amino acids .…”

Section: Figurementioning

confidence: 99%

Photocaged Quinone Methide Crosslinkers for Light‐Controlled Chemical Crosslinking of Protein–Protein and Protein–DNA Complexes

Cai

Sun

et al. 2019

Angew Chem Int Ed

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Small‐molecule crosslinkers are invaluable for probing biomolecular interactions and for crosslinking mass spectrometry. Existing chemical crosslinkers target only a small selection of amino acids, while conventional photo‐crosslinkers target almost all residues non‐specifically, complicating data analysis. Herein, we report photocaged quinone methide (PQM)‐based crosslinkers that target nine nucleophilic residues through Michael addition, including Gln, Arg, and Asn, which are inaccessible to existing chemical crosslinkers. PQM crosslinkers were used in vitro, in Escherichia coli, and in mammalian cells to crosslink dimeric proteins and endogenous membrane receptors. The heterobifunctional crosslinker NHQM could crosslink proteins to DNA, for which few crosslinkers exist. The photoactivatable reactivity of these crosslinkers and their ability to target multiple amino acids will enhance the use of chemical crosslinking for studies of protein–protein and protein–DNA networks and for structural biology.

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Section: Figurementioning

confidence: 99%

Photocaged Quinone Methide Crosslinkers for Light‐Controlled Chemical Crosslinking of Protein–Protein and Protein–DNA Complexes

Cai

Sun

et al. 2019

Angew Chem Int Ed

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“…Chemical cross‐linking combined with MS has matured into an alternative method to NMR and X‐ray crystallography for deriving three‐dimensional structures of proteins and protein assemblies . The introduction of covalent bonds between specific amino acid side chains via a linker molecule presents the principle of chemical cross‐linking and is the fundament for structure‐based MS.…”

Section: The Cross‐linking/ms Approachmentioning

confidence: 99%

Free radical‐initiated peptide sequencing (FRIPS)‐based cross‐linkers for improved peptide and protein structure analysis

Iacobucci

Schäfer

Sinz

2018

Mass Spectrometry Reviews

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Free radical-initiated peptide sequencing (FRIPS) has recently been introduced as an analytical strategy to create peptide radical ions in a predictable and effective way by collisional activation of specifically modified peptides ions. FRIPS is based on the unimolecular dissociation of open-shell ions and yields fragments that resemble those obtained by electron capture dissociation (ECD) or electron transfer dissociation (ETD). In this review article, we describe the fundamentals of FRIPS and highlight its fruitful combination with chemical cross-linking/mass spectrometry (MS) as a highly promising option to derive complementary structural information of peptides and proteins. FRIPS does not only yield exhaustive sequence information of cross-linked peptides, but also defines the exact cross-linking sites of the connected peptides. The development of more advanced FRIPS cross-linkers that extend the FRIPS-based cross-linking/MS approach to the study of large protein assemblies and protein interaction networks can be eagerly anticipated.

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“…Over the past two decades, mass spectrometry (MS)‐based proteomics has become an increasingly powerful technique to study proteins and their modifications (Eng et al, ; An et al, ; Zhang et al, ; Cox and Mann, ; Wollscheid et al, ; West et al, ; Nwosu et al, ; Butterfield et al, ; Aebersold and Mann, ; Glaskin et al, ; Suttapitugsakul et al, ; Yu and Huang, ). Protein modifications are extremely important in biological systems because they regulate nearly every cellular activity including gene expression, signal transduction, and cellular response to environmental cues (Mahal et al, ; Spiro, ; Varki et al, ; Wolfert and Boons, ).…”

Section: Introductionmentioning

confidence: 99%

Global and site‐specific analysis of protein glycosylation in complex biological systems with Mass Spectrometry

Xiao

Sun

Suttapitugsakul

et al. 2019

Mass Spectrometry Reviews

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Protein glycosylation is ubiquitous in biological systems and plays essential roles in many cellular events. Global and site‐specific analysis of glycoproteins in complex biological samples can advance our understanding of glycoprotein functions and cellular activities. However, it is extraordinarily challenging because of the low abundance of many glycoproteins and the heterogeneity of glycan structures. The emergence of mass spectrometry (MS)‐based proteomics has provided us an excellent opportunity to comprehensively study proteins and their modifications, including glycosylation. In this review, we first summarize major methods for glycopeptide/glycoprotein enrichment, followed by the chemical and enzymatic methods to generate a mass tag for glycosylation site identification. We next discuss the systematic and quantitative analysis of glycoprotein dynamics. Reversible protein glycosylation is dynamic, and systematic study of glycoprotein dynamics helps us gain insight into glycoprotein functions. The last part of this review focuses on the applications of MS‐based proteomics to study glycoproteins in different biological systems, including yeasts, plants, mice, human cells, and clinical samples. Intact glycopeptide analysis is also included in this section. Because of the importance of glycoproteins in complex biological systems, the field of glycoproteomics will continue to grow in the next decade. Innovative and effective MS‐based methods will exponentially advance glycoscience, and enable us to identify glycoproteins as effective biomarkers for disease detection and drug targets for disease treatment. © 2019 Wiley Periodicals, Inc. Mass Spec Rev 9999: XX–XX, 2019.

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Cross-Linking Mass Spectrometry: An Emerging Technology for Interactomics and Structural Biology

Abstract: Graphical Abstract

Cited by 279 publications

References 257 publications

Photocaged Quinone Methide Crosslinkers for Light‐Controlled Chemical Crosslinking of Protein–Protein and Protein–DNA Complexes

Photocaged Quinone Methide Crosslinkers for Light‐Controlled Chemical Crosslinking of Protein–Protein and Protein–DNA Complexes

Free radical‐initiated peptide sequencing (FRIPS)‐based cross‐linkers for improved peptide and protein structure analysis

Global and site‐specific analysis of protein glycosylation in complex biological systems with Mass Spectrometry

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