ArticleStructure (London, England : 1993)2012
Structural dynamics associated with intermediate formation in an archetypal conformational disease.
Article in Structure (London, England : 1993), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- The molecular species responsible for αThe FEBS journal · 2021Article
- Development of a small molecule that corrects misfolding and increases secretion of Z αEMBO molecular medicine · 2021Article
- High-resolution ex vivo NMR spectroscopy of human Z αNature communications · 2020Article
- The structural basis for Z αScience advances · 2020Article
- Intrahepatic heteropolymerization of M and Z alpha-1-antitrypsin.JCI insight · 2020Article
- Characterisation of a type II functionally-deficient variant of alpha-1-antitrypsin discovered in the general population.PloS one · 2019Article
- New Therapeutic Targets for Alpha-1 Antitrypsin Deficiency.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2018Article
- An antibody that prevents serpin polymerisation acts by inducing a novel allosteric behaviour.The Biochemical journal · 2016Article
- Smoothing a rugged protein folding landscape by sequence-based redesign.Scientific reports · 2016Article
- AFM Imaging Reveals Topographic Diversity of Wild Type and Z Variant Polymers of Human α1-Proteinase Inhibitor.PloS one · 2016Article
- 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.Protein science : a publication of the Protein Society · 2015Article
- An antibody raised against a pathogenic serpin variant induces mutant-like behaviour in the wild-type protein.The Biochemical journal · 2015Article
- Altered native stability is the dominant basis for susceptibility of α1-antitrypsin mutants to polymerization.The Biochemical journal · 2014Article
- Molecular mechanisms of disease-causing missense mutations.Journal of molecular biology · 2013Review
- Amphitrite: A program for processing travelling wave ion mobility mass spectrometry data.International journal of mass spectrometry · 2013Article
- Reactive centre loop mutants of α-1-antitrypsin reveal position-specific effects on intermediate formation along the polymerization pathway.Bioscience reports · 2013Article
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17 authors.
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Abstract
In conformational diseases, native protein conformers convert to pathological intermediates that polymerize. Structural characterization of these key intermediates is challenging. They are unstable and minimally populated in dynamic equilibria that may be perturbed by many analytical techniques. We have characterized a forme fruste deficiency variant of α(1)-antitrypsin (Lys154Asn) that forms polymers recapitulating the conformer-specific neo-epitope observed in polymers that form in vivo. Lys154Asn α(1)-antitrypsin populates an intermediate ensemble along the polymerization pathway at physiological temperatures. Nuclear magnetic resonance spectroscopy was used to report the structural and dynamic changes associated with this. Our data highlight an interaction network likely to regulate conformational change and do not support the recent contention that the disease-relevant intermediate is substantially unfolded. Conformational disease intermediates may best be defined using powerful but minimally perturbing techniques, mild disease mutants, and physiological conditions.
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