Rapid determination of quaternary protein structures in complex biological samples

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Bibtex

@article{4093fc5546154bc18c44503a0e6c30bc,
title = "Rapid determination of quaternary protein structures in complex biological samples",
abstract = "The understanding of complex biological systems is still hampered by limited knowledge of biologically relevant quaternary protein structures. Here, we demonstrate quaternary structure determination in biological samples using a combination of chemical cross-linking, high-resolution mass spectrometry and high-accuracy protein structure modeling. This approach, termed targeted cross-linking mass spectrometry (TX-MS), relies on computational structural models to score sets of targeted cross-linked peptide signals acquired using a combination of mass spectrometry acquisition techniques. We demonstrate the utility of TX-MS by creating a high-resolution quaternary model of a 1.8 MDa protein complex composed of a pathogen surface protein and ten human plasma proteins. The model is based on a dense network of cross-link distance constraints obtained directly in a mixture of human plasma and live bacteria. These results demonstrate that TX-MS can increase the applicability of flexible backbone docking algorithms to large protein complexes by providing rich cross-link distance information from complex biological samples.",
author = "Simon Hauri and Hamed Khakzad and Lotta Happonen and Johan Teleman and Johan Malmstr{\"o}m and Lars Malmstr{\"o}m",
year = "2019",
month = "1",
day = "14",
doi = "10.1038/s41467-018-07986-1",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}