MS2Assign, automated assignment and nomenclature of tandem mass spectra of chemically crosslinked peptides

Schilling, Birgit; Row, Richard H.; Gibson, Bradford W.; Guo, Xin Dong; Young, Malin M.

doi:10.1016/s1044-0305(03)00327-1

Cited by 259 publications

(396 citation statements)

References 26 publications

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“…Once distinguished and identified, collisionally activated dissociation (CAD) experiments on these species are performed to sequence the peptide or peptides. Structural assignment of the crosslinked peptides is still not routine despite the emergence of several sequencing algorithms [17][18][19][20][21][22]. In fact, one of the main pitfalls of mass spectrometric strategies for examination of crosslinked peptides is the lack of comprehensive rules for interpretation of the product ion spectra.…”

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confidence: 99%

“…Despite the enormous number of investigations that have elucidated the fragmentation pathways of conventional tryptic peptides, to date only a few studies have focused on mapping the dissociation trends of crosslinked peptides in a systematic fashion [20,23,24]. Initial work by Schilling et al demonstrated that dissociation of intermolecularly crosslinked peptides typically resulted in amide bond cleavage of one peptide, with the crosslink and second peptide acting as a modification [20].…”

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confidence: 99%

“…Initial work by Schilling et al demonstrated that dissociation of intermolecularly crosslinked peptides typically resulted in amide bond cleavage of one peptide, with the crosslink and second peptide acting as a modification [20]. In addition, they observed product ions unique to crosslinked peptides, including two cleavage fragment ions such as b/b ions, in which two b-type fragment ions were linked together.…”

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Impact of proline and aspartic acid residues on the dissociation of intermolecularly crosslinked peptides

Gardner

Brodbelt

2008

J. Am. Soc. Mass Spectrom.

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The dissociation of intermolecularly crosslinked peptides was evaluated for a series of peptides with proline or aspartic acid residues positioned adjacent to the crosslinking sites (lysine residues). The peptides were crosslinked with either disuccinimidyl suberate (DSS) or disuccinimidyl L-tartrate (DST), and the influence of proline and aspartic acid residues on the fragmentation patterns were investigated for precursor ions with and without a mobile proton. Collisionally activated dissociation (CAD) spectra of aspartic acid-containing crosslinked peptide ions, doublycharged with both protons sequestered, were dominated by cleavage C-terminal to the Asp residue, similar to that of unmodified peptides. The proline-containing crosslinked peptides exhibited a high degree of internal ion formation, with the resulting product ions having an N-terminal proline residue. Upon dissociation of the doubly-charged crosslinked peptides, twenty to fifty percent of the fragment ion abundance was accounted for by multiple cleavage products. Crosslinked peptides possessing a mobile proton yielded almost a full series of b-and y-type fragment ions, with only proline-directed fragments still observed at high abundances. Interestingly, the crosslinked peptides exhibited a tendency to dissociate at the amide bond C-terminal to the crosslinked lysine residue, relative to the N-terminal side. One could envision updating computer algorithms to include these crosslinker specific product ions-particularly for precursor ions with localized protons-that provide complementary and confirmatory information, to offer more confident identification of both the crosslinked peptides and the location of the crosslink, as well as affording predictive guidelines for interpretation of the product-ion spectra of crosslinked peptides. (J

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Impact of proline and aspartic acid residues on the dissociation of intermolecularly crosslinked peptides

Gardner

Brodbelt

2008

J. Am. Soc. Mass Spectrom.

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“…Using these 15 constraints it was possible to assign the FGF2 to the correct ␤-trefoil fold family, from among a large set of structures predicted using threading techniques. The name MS3D has been proposed for the study of protein 3-dimensional structure using chemical cross-linking and mass spectrometry [5].All of the subsequent recent work published on intra-molecular cross-linking for MS3D studies has employed similar, commercially available primary amine selective reagents that can cross-link lysine residues to other lysine residues or the amino terminus [6 -10]. In our own recent work, we showed that a top down approach to the localization of cross-links using FTMS could be applied to localize three cross-links in ubiquitin [7], and in a more recent publication we showed that the distance constraints can be improved by using a series of cross-linkers of different lengths [6].…”

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Strategy for selective chemical cross-linking of tyrosine and lysine residues

Leavell

Novák

Behrens

et al. 2004

J. Am. Soc. Mass Spectrom.

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Chemical cross-linking of proteins combined with mass spectral analysis is a powerful technique that can be utilized to yield protein structural information, such as the spatial arrangement of multi-protein complexes or the folding of monomeric proteins. The succinimidyl ester cross-linking reagents are commonly used to cross-link primary amine-containing amino acids (N-terminus and lysine). However, in this study they were used to react with tyrosines as well, which allowed for the formation of cross-links between two primary amines, one primary amine and one tyrosine, or two tyrosines. This result is extremely important to the chemical cross-linking community for two reasons: (1) all possible cross-linked residues must be considered when analyzing data from these experiments to generate correct distance constraints and structural information, and (2) utilizing the versatility of these cross-linking reagents allows more information content to be generated from a single cross-linking reagent, which may increase the number of cross-links obtained in the experiment. Herein, we study the reactivity of the succinimidyl ester labeling and cross-linking reagents with angiotensin I and oxidized insulin ␤-chain. Using the succinimidyl acetate labeling reagent, the reactivity of the N-terminus was found to be greater than either lysine or tyrosine. However, a selectivity of the cross-linking reagent was observed for either tyrosine or lysine depending on the pH of the reaction solution. In acidic pH, it was observed that tyrosine was more reactive, while in alkaline pH lysine was more reactive. Exploiting this selectivity predominantly N-terminustyrosine or tyrosine-tyrosine cross-links were favored at acidic pH, while N-terminus-tyrosine or tyrosine-lysine cross-links were favored at alkaline pH. I nter-molecular chemical cross-linking has a long history as a tool for the study of the quaternary structure of protein complexes [1,2], and many years ago it was suggested that intra-molecular cross-linking could be used as a method of obtaining distance constraints that would be useful in developing structural models of proteins [3]. However, the promise of intra-molecular crosslinking for structural modeling has only recently been enabled by state of the art mass spectrometric methods that make determination of the cross-linked residues in a protein practical on a reasonable time scale and with small quantities of protein. The first study to derive a sufficient number of intra-molecular distance constraints to develop a structural model for a protein used fibroblast growth factor 2 (FGF-2) as a test case [4]. FGF-2 is a 17 kDa protein, which has 14 lysines evenly dispersed in its 155 residue sequence. Using only the commercially available primary amine reactive cross-linker bis(sulfosuccinimidyl) suberate, 18 cross-links were found in FGF-2 in this study, of which 15 provided useful distance constraints for determining the fold family of the protein. Using these 15 constraints it was possible to assign the FGF2 to the corr...

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Using pLink to Analyze Cross‐Linked Peptides

Fan

Meng

et al. 2015

CP in Bioinformatics

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pLink is a search engine for high‐throughput identification of cross‐linked peptides from their tandem mass spectra, which is the data‐analysis step in chemical cross‐linking of proteins coupled with mass spectrometry analysis. pLink has accumulated more than 200 registered users from all over the world since its first release in 2012. After 2 years of continual development, a new version of pLink has been released, which is at least 40 times faster, more versatile, and more user‐friendly. Also, the function of the new pLink has been expanded to identifying endogenous protein cross‐linking sites such as disulfide bonds and SUMO (Small Ubiquitin‐like MOdifier) modification sites. Integrated into the new version are two accessory tools: pLabel, to annotate spectra of cross‐linked peptides for visual inspection and publication, and pConfig, to assist users in setting up search parameters. Here, we provide detailed guidance on running a database search for identification of protein cross‐links using the 2014 version of pLink. © 2015 by John Wiley & Sons, Inc.

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MS2Assign, automated assignment and nomenclature of tandem mass spectra of chemically crosslinked peptides

Cited by 259 publications

References 26 publications

Impact of proline and aspartic acid residues on the dissociation of intermolecularly crosslinked peptides

Impact of proline and aspartic acid residues on the dissociation of intermolecularly crosslinked peptides

Strategy for selective chemical cross-linking of tyrosine and lysine residues

Using pLink to Analyze Cross‐Linked Peptides

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