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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-7916671 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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