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Detailed Structure and Pathophysiological Roles of the IgA-Albumin Complex in Multiple Myeloma

Immunoglobulin A (IgA)-albumin complexes may be associated with pathophysiology of multiple myeloma, although the etiology is not clear. Detailed structural analyses of these protein–protein complexes may contribute to our understanding of the pathophysiology of this disease. We analyzed the structu...

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Autores principales: Kawata, Yuki, Hirano, Hisashi, Takahashi, Ren, Miyano, Yukari, Kimura, Ayuko, Sato, Natsumi, Morita, Yukio, Kimura, Hirokazu, Fujita, Kiyotaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916671/
https://www.ncbi.nlm.nih.gov/pubmed/33578917
http://dx.doi.org/10.3390/ijms22041766
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author Kawata, Yuki
Hirano, Hisashi
Takahashi, Ren
Miyano, Yukari
Kimura, Ayuko
Sato, Natsumi
Morita, Yukio
Kimura, Hirokazu
Fujita, Kiyotaka
author_facet Kawata, Yuki
Hirano, Hisashi
Takahashi, Ren
Miyano, Yukari
Kimura, Ayuko
Sato, Natsumi
Morita, Yukio
Kimura, Hirokazu
Fujita, Kiyotaka
author_sort Kawata, Yuki
collection PubMed
description Immunoglobulin A (IgA)-albumin complexes may be associated with pathophysiology of multiple myeloma, although the etiology is not clear. Detailed structural analyses of these protein–protein complexes may contribute to our understanding of the pathophysiology of this disease. We analyzed the structure of the IgA-albumin complex using various electrophoresis, mass spectrometry, and in silico techniques. The data based on the electrophoresis and mass spectrometry showed that IgA in the sera of patients was dimeric, linked via the J chain. Only dimeric IgA can bind to albumin molecules leading to IgA-albumin complexes, although both monomeric and dimeric forms of IgA were present in the sera. Molecular interaction analyses in silico implied that dimeric IgA and albumin interacted not only via disulfide bond formation, but also via noncovalent bonds. Disulfide bonds were predicted between Cys34 of albumin and Cys311 of IgA, resulting in an oxidized form of albumin. Furthermore, complex formation prolongs the half-life of IgA molecules in the IgA-albumin complex, leading to excessive glycation of IgA molecules and affects the accumulation of IgA in serum. These findings may demonstrate why complications such as hyperviscosity syndrome occur more often in patients with IgA dimer producing multiple myeloma.
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spelling pubmed-79166712021-03-01 Detailed Structure and Pathophysiological Roles of the IgA-Albumin Complex in Multiple Myeloma Kawata, Yuki Hirano, Hisashi Takahashi, Ren Miyano, Yukari Kimura, Ayuko Sato, Natsumi Morita, Yukio Kimura, Hirokazu Fujita, Kiyotaka Int J Mol Sci Article Immunoglobulin A (IgA)-albumin complexes may be associated with pathophysiology of multiple myeloma, although the etiology is not clear. Detailed structural analyses of these protein–protein complexes may contribute to our understanding of the pathophysiology of this disease. We analyzed the structure of the IgA-albumin complex using various electrophoresis, mass spectrometry, and in silico techniques. The data based on the electrophoresis and mass spectrometry showed that IgA in the sera of patients was dimeric, linked via the J chain. Only dimeric IgA can bind to albumin molecules leading to IgA-albumin complexes, although both monomeric and dimeric forms of IgA were present in the sera. Molecular interaction analyses in silico implied that dimeric IgA and albumin interacted not only via disulfide bond formation, but also via noncovalent bonds. Disulfide bonds were predicted between Cys34 of albumin and Cys311 of IgA, resulting in an oxidized form of albumin. Furthermore, complex formation prolongs the half-life of IgA molecules in the IgA-albumin complex, leading to excessive glycation of IgA molecules and affects the accumulation of IgA in serum. These findings may demonstrate why complications such as hyperviscosity syndrome occur more often in patients with IgA dimer producing multiple myeloma. MDPI 2021-02-10 /pmc/articles/PMC7916671/ /pubmed/33578917 http://dx.doi.org/10.3390/ijms22041766 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kawata, Yuki
Hirano, Hisashi
Takahashi, Ren
Miyano, Yukari
Kimura, Ayuko
Sato, Natsumi
Morita, Yukio
Kimura, Hirokazu
Fujita, Kiyotaka
Detailed Structure and Pathophysiological Roles of the IgA-Albumin Complex in Multiple Myeloma
title Detailed Structure and Pathophysiological Roles of the IgA-Albumin Complex in Multiple Myeloma
title_full Detailed Structure and Pathophysiological Roles of the IgA-Albumin Complex in Multiple Myeloma
title_fullStr Detailed Structure and Pathophysiological Roles of the IgA-Albumin Complex in Multiple Myeloma
title_full_unstemmed Detailed Structure and Pathophysiological Roles of the IgA-Albumin Complex in Multiple Myeloma
title_short Detailed Structure and Pathophysiological Roles of the IgA-Albumin Complex in Multiple Myeloma
title_sort detailed structure and pathophysiological roles of the iga-albumin complex in multiple myeloma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916671/
https://www.ncbi.nlm.nih.gov/pubmed/33578917
http://dx.doi.org/10.3390/ijms22041766
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