ArticleProtein science : a publication of the Protein Society2015
An integrative approach combining ion mobility mass spectrometry, X-ray crystallography, and nuclear magnetic resonance spectroscopy to study the conformational dynamics of α1 -antitrypsin upon ligand binding.
Article in Protein science : a publication of the Protein Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Native and Ion Mobility Mass Spectrometry Characterization of Alpha 1 Antitrypsin Variants and Oligomers.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Native and Ion Mobility Mass Spectrometry Characterization of Alpha 1 Antitrypsin Variants and Oligomers.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Mass spectrometers as cryoEM grid preparation instruments.Current opinion in structural biology · 2023Review
- A Flexible, Modular Platform for Multidimensional Ion Mobility of Native-like Ions.Journal of the American Society for Mass Spectrometry · 2023Article
- Capturing the conversion of the pathogenic alpha-1-antitrypsin fold by ATF6 enhanced proteostasis.Cell chemical biology · 2023Article
- Linking Gas-Phase and Solution-Phase Protein Unfolding via Mobile Proton Simulations.Analytical chemistry · 2022Article
- Structural mass spectrometry decodes domain interaction and dynamics of the full-length Human Histone Deacetylase 2.Biochimica et biophysica acta. Proteins and proteomics · 2022Article
- Cyclic Ion Mobility-Collision Activation Experiments Elucidate Protein Behavior in the Gas Phase.Journal of the American Society for Mass Spectrometry · 2021Article
- High-resolution ex vivo NMR spectroscopy of human Z αNature communications · 2020Article
- Post-Translational Modifications of Circulating Alpha-1-Antitrypsin Protein.International journal of molecular sciences · 2020Review
- The structural basis for Z αScience advances · 2020Article
- Gas Phase Stability of Protein Ions in a Cyclic Ion Mobility Spectrometry Traveling Wave Device.Analytical chemistry · 2019Article
- Principles of Ion Selection, Alignment, and Focusing in Tandem Ion Mobility Implemented Using Structures for Lossless Ion Manipulations (SLIM).Journal of the American Society for Mass Spectrometry · 2019Article
- New Therapeutic Targets for Alpha-1 Antitrypsin Deficiency.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2018Article
- Structural and functional adaptation of Haloferax volcanii TFEα/β.Nucleic acids research · 2018Article
- Magnifying ion mobility spectrometry-mass spectrometry measurements for biomolecular structure studies.Current opinion in chemical biology · 2018Review
- AFM Imaging Reveals Topographic Diversity of Wild Type and Z Variant Polymers of Human α1-Proteinase Inhibitor.PloS one · 2016Article
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12 authors.
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Abstract
Native mass spectrometry (MS) methods permit the study of multiple protein species within solution equilibria, whereas ion mobility (IM)-MS can report on conformational behavior of specific states. We used IM-MS to study a conformationally labile protein (α1 -antitrypsin) that undergoes pathological polymerization in the context of point mutations. The folded, native state of the Z-variant remains highly polymerogenic in physiological conditions despite only minor thermodynamic destabilization relative to the wild-type variant. Various data implicate kinetic instability (conformational lability within a native state ensemble) as the basis of Z α1 -antitrypsin polymerogenicity. We show the ability of IM-MS to track such disease-relevant conformational behavior in detail by studying the effects of peptide binding on α1 -antitrypsin conformation and dynamics. IM-MS is, therefore, an ideal platform for the screening of compounds that result in therapeutically beneficial kinetic stabilization of native α1 -antitrypsin. Our findings are confirmed with high-resolution X-ray crystallographic and nuclear magnetic resonance spectroscopic studies of the same event, which together dissect structural changes from dynamic effects caused by peptide binding at a residue-specific level. IM-MS methods, therefore, have great potential for further study of biologically relevant thermodynamic and kinetic instability of proteins and provide rapid and multidimensional characterization of ligand interactions of therapeutic interest.
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