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Article Dans Une Revue Nature Communications Année : 2019

Rapid determination of quaternary protein structures in complex biological samples

Simon Hauri
Lotta Happonen
  • Fonction : Auteur
Johan Teleman
  • Fonction : Auteur
Johan Malmström

Résumé

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, highresolution 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.
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Dates et versions

hal-04429464 , version 1 (31-01-2024)

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Simon Hauri, Hamed Khakzad, Lotta Happonen, Johan Teleman, Johan Malmström, et al.. Rapid determination of quaternary protein structures in complex biological samples. Nature Communications, 2019, 10 (1), pp.192. ⟨10.1038/s41467-018-07986-1⟩. ⟨hal-04429464⟩
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