ArticleThe Journal of biological chemistry2014
Identification of a point mutation impairing the binding between aquaporin-4 and neuromyelitis optica autoantibodies.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 32 citations in OpenAlex.
- Comparative Analysis of T-Cell Responses to Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein in Inflammatory Demyelinating Central Nervous System Diseases.Frontiers in immunology · 2020Article
- Article
- Massive transcriptome sequencing of human spinal cord tissues provides new insights into motor neuron degeneration in ALS.Scientific reports · 2017Article
- Computing osmotic permeabilities of aquaporins AQP4, AQP5, and GlpF from near-equilibrium simulations.Biochimica et biophysica acta. Biomembranes · 2017Article
- Comparative molecular dynamics study of neuromyelitis optica-immunoglobulin G binding to aquaporin-4 extracellular domains.Biochimica et biophysica acta. Biomembranes · 2017Article
- Mapping autoantigen epitopes: molecular insights into autoantibody-associated disorders of the nervous system.Journal of neuroinflammation · 2016Review
- Human Aquaporin-4 and Molecular Modeling: Historical Perspective and View to the Future.International journal of molecular sciences · 2016Review
- Characterization of the binding pattern of human aquaporin-4 autoantibodies in patients with neuromyelitis optica spectrum disorders.Journal of neuroinflammation · 2016Article
- Mutation of N-linked glycosylation at Asn548 in CD133 decreases its ability to promote hepatoma cell growth.Oncotarget · 2015Article
- Mutagenesis of the aquaporin 4 extracellular domains defines restricted binding patterns of pathogenic neuromyelitis optica IgG.The Journal of biological chemistry · 2015Article
- Development of an Aquaporin-4 Orthogonal Array of Particle-Based ELISA for Neuromyelitis Optica Autoantibodies Detection.PloS one · 2015Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuromyelitis optica (NMO) is characterized by the presence of pathogenic autoantibodies (NMO-IgGs) against supra-molecular assemblies of aquaporin-4 (AQP4), known as orthogonal array of particles (OAPs). NMO-IgGs have a polyclonal origin and recognize different conformational epitopes involving extracellular AQP4 loops A, C, and E. Here we hypothesize a pivotal role for AQP4 transmembrane regions (TMs) in epitope assembly. On the basis of multialignment analysis, mutagenesis, NMO-IgG binding, and cytotoxicity assay, we have disclosed the key role of aspartate 69 (Asp(69)) of TM2 for NMO-IgG epitope assembly. Mutation of Asp(69) to histidine severely impairs NMO-IgG binding for 85.7% of the NMO patient sera analyzed here. Although Blue Native-PAGE, total internal reflection fluorescence microscopy, and water transport assays indicate that the OAP Asp(69) mutant is similar in structure and function to the wild type, molecular dynamic simulations have revealed that the D(69)H mutation has the effect of altering the structural rearrangements of extracellular loop A. In conclusion, Asp(69) is crucial for the spatial control of loop A, the particular molecular conformation of which enables the assembly of NMO-IgG epitopes. These findings provide additional clues for new strategies for NMO treatment and a wealth of information to better approach NMO pathogenesis.
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