ArticleBiochemistry2012
Effects of the Iowa and Milano mutations on apolipoprotein A-I structure and dynamics determined by hydrogen exchange and mass spectrometry.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- The Positive Side of the Alzheimer's Disease Amyloid Cross-Interactions: The Case of the Aβ 1-42 Peptide with Tau, TTR, CysC, and ApoA1.Molecules (Basel, Switzerland) · 2020Review
- Mechanisms of aggregation and fibril formation of the amyloidogenic N-terminal fragment of apolipoprotein A-I.The Journal of biological chemistry · 2019Article
- A consensus model of human apolipoprotein A-I in its monomeric and lipid-free state.Nature structural & molecular biology · 2017Article
- Synchrotron radiation circular dichroism spectroscopy reveals structural divergences in HDL-bound apoA-I variants.Scientific reports · 2017Article
- Helical structure, stability, and dynamics in human apolipoprotein E3 and E4 by hydrogen exchange and mass spectrometry.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Structural Stability and Local Dynamics in Disease-Causing Mutants of Human Apolipoprotein A-I: What Makes the Protein Amyloidogenic?Journal of molecular biology · 2016Article
- Amyloidogenic Mutation Promotes Fibril Formation of the N-terminal Apolipoprotein A-I on Lipid Membranes.The Journal of biological chemistry · 2015Article
- Membrane effects of N-terminal fragment of apolipoprotein A-I: a fluorescent probe study.Journal of fluorescence · 2015Article
- Applications of hydrogen/deuterium exchange MS from 2012 to 2014.Analytical chemistry · 2015Review
- Amyloid-Forming Properties of Human Apolipoproteins: Sequence Analyses and Structural Insights.Advances in experimental medicine and biology · 2015Review
- Article
- QUDeX-MS: hydrogen/deuterium exchange calculation for mass spectra with resolved isotopic fine structure.BMC bioinformatics · 2014Article
- Amyloidogenic mutations in human apolipoprotein A-I are not necessarily destabilizing - a common mechanism of apolipoprotein A-I misfolding in familial amyloidosis and atherosclerosis.The FEBS journal · 2014Article
- Structural basis for distinct functions of the naturally occurring Cys mutants of human apolipoprotein A-I.Journal of lipid research · 2013Review
- New insights into the determination of HDL structure by apolipoproteins: Thematic review series: high density lipoprotein structure, function, and metabolism.Journal of lipid research · 2013Review
- Comparison of apoA-I helical structure and stability in discoidal and spherical HDL particles by HX and mass spectrometry.Journal of lipid research · 2013Article
- Mass spectrometry-based methods to study protein architecture and dynamics.Protein science : a publication of the Protein Society · 2013Review
- Dual role of an N-terminal amyloidogenic mutation in apolipoprotein A-I: destabilization of helix bundle and enhancement of fibril formation.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The Iowa point mutation in apolipoprotein A-I (G26R) leads to a systemic amyloidosis condition, and the Milano mutation (R173C) is associated with hypoalphalipoproteinemia, a reduced plasma level of high-density lipoprotein. To probe the structural effects that lead to these outcomes, we used amide hydrogen-deuterium exchange coupled with a fragment separation/mass spectrometry analysis (HX MS). The Iowa mutation inserts an arginine residue into the nonpolar face of an α-helix that spans residues 7-44 and causes changes in structure and structural dynamics. This helix unfolds, and other helices in the N-terminal helix bundle domain are destabilized. The segment encompassing residues 116-158, largely unstructured in wild-type apolipoprotein A-I, becomes helical. The helix spanning residues 81-115 is destabilized by 2 kcal/mol, increasing the small fraction of time it is transiently unfolded to ≥1%, which allows proteolysis at residue 83 in vivo over time, releasing an amyloid-forming peptide. The Milano mutation situated on the polar face of the helix spanning residues 147-178 destabilizes the helix bundle domain only moderately, but enough to allow cysteine-mediated dimerization that leads to the altered functionality of this variant. These results show how the HX MS approach can provide a powerful means of monitoring, in a nonperturbing way and at close to amino acid resolution, the structural, dynamic, and energetic consequences of biologically interesting point mutations.
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