A General Method for Targeted Quantitative Cross-Linking Mass Spectrometry

Chavez, J. D., Eng, J. K., Schweppe, D. K., Cilia, M., Rivera, K., Zhong, X., Wu, X., Allen, T., Khurgel, M., Kumar, A., Lampropoulos, A., Larsson, M., Maity, S., Morozov, Y., Pathmasiri, W., Perez-Neut, M., Pineyro-Ruiz, C., Polina, E., Post, S., Rider, M., Tokmina-Roszyk, D., Tyson, K., Vieira Parrine Sant'Ana, D., Bruce, J. E. (December 2016) A General Method for Targeted Quantitative Cross-Linking Mass Spectrometry. PLoS One, 11 (12). e0167547. ISSN 1932-6203

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URL: https://www.ncbi.nlm.nih.gov/pubmed/27997545
DOI: 10.1371/journal.pone.0167547

Abstract

Chemical cross-linking mass spectrometry (XL-MS) provides protein structural information by identifying covalently linked proximal amino acid residues on protein surfaces. The information gained by this technique is complementary to other structural biology methods such as x-ray crystallography, NMR and cryo-electron microscopy[1]. The extension of traditional quantitative proteomics methods with chemical cross-linking can provide information on the structural dynamics of protein structures and protein complexes. The identification and quantitation of cross-linked peptides remains challenging for the general community, requiring specialized expertise ultimately limiting more widespread adoption of the technique. We describe a general method for targeted quantitative mass spectrometric analysis of cross-linked peptide pairs. We report the adaptation of the widely used, open source software package Skyline, for the analysis of quantitative XL-MS data as a means for data analysis and sharing of methods. We demonstrate the utility and robustness of the method with a cross-laboratory study and present data that is supported by and validates previously published data on quantified cross-linked peptide pairs. This advance provides an easy to use resource so that any lab with access to a LC-MS system capable of performing targeted quantitative analysis can quickly and accurately measure dynamic changes in protein structure and protein interactions.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics
Investigative techniques and equipment > spectroscopy > mass spectrometry
CSHL Authors:
Communities: CSHL labs > Pappin lab
Depositing User: Matt Covey
Date: 20 December 2016
Date Deposited: 21 Jul 2017 15:56
Last Modified: 03 Nov 2017 15:56
PMCID: PMC5172568
Related URLs:
URI: https://repository.cshl.edu/id/eprint/35060

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