Rapid determination of quaternary protein structures in complex biological samples
Hauri, Simon LU ; Khakzad, Hamed ; Happonen, Lotta LU ; Teleman, Johan LU ; Malmström, Johan LU
and Malmström, Lars
LU
(2019)
In Nature Communications
10.
- 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... (More)
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.
(Less)
- author
- Hauri, Simon
LU
; Khakzad, Hamed
; Happonen, Lotta
LU
; Teleman, Johan
LU
; Malmström, Johan
LU
and Malmström, Lars
LU
- organization
- publishing date
- 2019-01-14
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 10
- article number
- 192
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85060008705
- pmid:30643114
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-018-07986-1
- language
- English
- LU publication?
- yes
- id
- 4093fc55-4615-4bc1-8c44-503a0e6c30bc
- date added to LUP
- 2019-01-22 10:51:56
- date last changed
- 2024-06-12 05:33:09
@article{4093fc55-4615-4bc1-8c44-503a0e6c30bc,
abstract = {{<p>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.</p>}},
author = {{Hauri, Simon and Khakzad, Hamed and Happonen, Lotta and Teleman, Johan and Malmström, Johan and Malmström, Lars}},
issn = {{2041-1723}},
language = {{eng}},
month = {{01}},
publisher = {{Nature Publishing Group}},
series = {{Nature Communications}},
title = {{Rapid determination of quaternary protein structures in complex biological samples}},
url = {{http://dx.doi.org/10.1038/s41467-018-07986-1}},
doi = {{10.1038/s41467-018-07986-1}},
volume = {{10}},
year = {{2019}},
}