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Rapid determination of quaternary protein structures in complex biological samples
by
Teleman, Johan
, Khakzad, Hamed
, Malmström, Lars
, Hauri, Simon
, Happonen, Lotta
, Malmström, Johan
in
631/114/2411
/ 631/1647/296
/ 631/45/475/2290
/ 631/535/1267
/ 82/58
/ Algorithms
/ Basic Medicine
/ Biological properties
/ Biological samples
/ Blood plasma
/ Blood Proteins - chemistry
/ Blood Proteins - isolation & purification
/ Chromatography, Reverse-Phase - instrumentation
/ Chromatography, Reverse-Phase - methods
/ Computer applications
/ Cross-Linking Reagents - chemistry
/ Crosslinking
/ Docking
/ Healthy Volunteers
/ High resolution
/ Humanities and Social Sciences
/ Humans
/ Life Sciences
/ Läkemedelskemi
/ Mass spectrometry
/ Mass spectroscopy
/ Medical and Health Sciences
/ Medicin och hälsovetenskap
/ Medicinal Chemistry
/ Medicinska och farmaceutiska grundvetenskaper
/ Model accuracy
/ Molecular Docking Simulation - methods
/ multidisciplinary
/ Multiprotein Complexes - chemistry
/ Organic chemistry
/ Plasma
/ Plasma proteins
/ Protein structure
/ Protein Structure, Quaternary
/ Proteins
/ Quaternary structure
/ Recombinant Proteins - chemistry
/ Recombinant Proteins - isolation & purification
/ Science
/ Science (multidisciplinary)
/ Scientific imaging
/ Software
/ Spectroscopy
/ Structural models
/ Tandem Mass Spectrometry - instrumentation
/ Tandem Mass Spectrometry - methods
2019
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Rapid determination of quaternary protein structures in complex biological samples
by
Teleman, Johan
, Khakzad, Hamed
, Malmström, Lars
, Hauri, Simon
, Happonen, Lotta
, Malmström, Johan
in
631/114/2411
/ 631/1647/296
/ 631/45/475/2290
/ 631/535/1267
/ 82/58
/ Algorithms
/ Basic Medicine
/ Biological properties
/ Biological samples
/ Blood plasma
/ Blood Proteins - chemistry
/ Blood Proteins - isolation & purification
/ Chromatography, Reverse-Phase - instrumentation
/ Chromatography, Reverse-Phase - methods
/ Computer applications
/ Cross-Linking Reagents - chemistry
/ Crosslinking
/ Docking
/ Healthy Volunteers
/ High resolution
/ Humanities and Social Sciences
/ Humans
/ Life Sciences
/ Läkemedelskemi
/ Mass spectrometry
/ Mass spectroscopy
/ Medical and Health Sciences
/ Medicin och hälsovetenskap
/ Medicinal Chemistry
/ Medicinska och farmaceutiska grundvetenskaper
/ Model accuracy
/ Molecular Docking Simulation - methods
/ multidisciplinary
/ Multiprotein Complexes - chemistry
/ Organic chemistry
/ Plasma
/ Plasma proteins
/ Protein structure
/ Protein Structure, Quaternary
/ Proteins
/ Quaternary structure
/ Recombinant Proteins - chemistry
/ Recombinant Proteins - isolation & purification
/ Science
/ Science (multidisciplinary)
/ Scientific imaging
/ Software
/ Spectroscopy
/ Structural models
/ Tandem Mass Spectrometry - instrumentation
/ Tandem Mass Spectrometry - methods
2019
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Rapid determination of quaternary protein structures in complex biological samples
by
Teleman, Johan
, Khakzad, Hamed
, Malmström, Lars
, Hauri, Simon
, Happonen, Lotta
, Malmström, Johan
in
631/114/2411
/ 631/1647/296
/ 631/45/475/2290
/ 631/535/1267
/ 82/58
/ Algorithms
/ Basic Medicine
/ Biological properties
/ Biological samples
/ Blood plasma
/ Blood Proteins - chemistry
/ Blood Proteins - isolation & purification
/ Chromatography, Reverse-Phase - instrumentation
/ Chromatography, Reverse-Phase - methods
/ Computer applications
/ Cross-Linking Reagents - chemistry
/ Crosslinking
/ Docking
/ Healthy Volunteers
/ High resolution
/ Humanities and Social Sciences
/ Humans
/ Life Sciences
/ Läkemedelskemi
/ Mass spectrometry
/ Mass spectroscopy
/ Medical and Health Sciences
/ Medicin och hälsovetenskap
/ Medicinal Chemistry
/ Medicinska och farmaceutiska grundvetenskaper
/ Model accuracy
/ Molecular Docking Simulation - methods
/ multidisciplinary
/ Multiprotein Complexes - chemistry
/ Organic chemistry
/ Plasma
/ Plasma proteins
/ Protein structure
/ Protein Structure, Quaternary
/ Proteins
/ Quaternary structure
/ Recombinant Proteins - chemistry
/ Recombinant Proteins - isolation & purification
/ Science
/ Science (multidisciplinary)
/ Scientific imaging
/ Software
/ Spectroscopy
/ Structural models
/ Tandem Mass Spectrometry - instrumentation
/ Tandem Mass Spectrometry - methods
2019
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Rapid determination of quaternary protein structures in complex biological samples
Journal Article
Rapid determination of quaternary protein structures in complex biological samples
2019
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Overview
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.
Protein structure determination in complex biological samples is still challenging. Here, the authors develop a computational modeling-guided cross-linking mass spectrometry method, obtaining a high-resolution model of a 1.8 MDa protein assembly from cross-links detected in a mixture of human plasma and bacteria.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 82/58
/ Blood Proteins - isolation & purification
/ Chromatography, Reverse-Phase - instrumentation
/ Chromatography, Reverse-Phase - methods
/ Cross-Linking Reagents - chemistry
/ Docking
/ Humanities and Social Sciences
/ Humans
/ Medicinska och farmaceutiska grundvetenskaper
/ Molecular Docking Simulation - methods
/ Multiprotein Complexes - chemistry
/ Plasma
/ Protein Structure, Quaternary
/ Proteins
/ Recombinant Proteins - chemistry
/ Recombinant Proteins - isolation & purification
/ Science
/ Software
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