Dystrophin hydrophobic regions in the pathogenesis of Duchenne and Becker muscular dystrophies
The aim of our study was to determine the role of dystrophin hydrophobic regions in the pathogenesis of Duchenne (DMD) and Becker (BMD) muscular dystrophies, by the Kyte-Doolittle scale mean hydrophobicity profile and 3D molecular models. A total of 1038 cases diagnosed with DMD or BMD with the in-f...
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| Format: | Article |
| Language: | English |
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Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2015-05-01
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| Series: | Biomolecules & Biomedicine |
| Subjects: | |
| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/300 |
| _version_ | 1797260876710936576 |
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| author | Yingyin Liang Songlin Chen Jianzong Zhu Xiangxue Zhou Chen Yang Lu Yao Cheng Zhang |
| author_facet | Yingyin Liang Songlin Chen Jianzong Zhu Xiangxue Zhou Chen Yang Lu Yao Cheng Zhang |
| author_sort | Yingyin Liang |
| collection | DOAJ |
| description | The aim of our study was to determine the role of dystrophin hydrophobic regions in the pathogenesis of Duchenne (DMD) and Becker (BMD) muscular dystrophies, by the Kyte-Doolittle scale mean hydrophobicity profile and 3D molecular models. A total of 1038 cases diagnosed with DMD or BMD with the in-frame mutation were collected in our hospital and the Leiden DMD information database in the period 2002-2013. Correlation between clinical types and genotypes were determined on the basis of these two sources. In addition, the Kyte-Doolittle scale mean hydrophobicity of dystrophin was analyzed using BioEdit software and the models of the hydrophobic domains of dystrophin were constructed. The presence of four hydrophobic regions is confirmed. They include the calponin homology CH2 domain on the actin-binding domain (ABD), spectrin-type repeat 16, hinge III and the EF Hand domain. The severe symptoms of DMD usually develop as a result of the mutational disruption in the hydrophobic regions I, II and IV of dystrophin – those that bind associated proteins of the dystrophin-glycoprotein complex (DGC). On the other hand, when the hydrophobic region III is deleted, the connection of the ordered repeat domains of the central rod domain remains intact, resulting in the less severe clinical presentation. We conclude that mutational changes in the structure of hydrophobic regions of dystrophin play an important role in the pathogenesis of DMD.
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| first_indexed | 2024-04-24T23:32:17Z |
| format | Article |
| id | doaj.art-450a01cee5d64715b07eb675552471f3 |
| institution | Directory Open Access Journal |
| issn | 2831-0896 2831-090X |
| language | English |
| last_indexed | 2024-04-24T23:32:17Z |
| publishDate | 2015-05-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
| record_format | Article |
| series | Biomolecules & Biomedicine |
| spelling | doaj.art-450a01cee5d64715b07eb675552471f32024-03-15T14:32:59ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2015-05-0115210.17305/bjbms.2015.30049Dystrophin hydrophobic regions in the pathogenesis of Duchenne and Becker muscular dystrophiesYingyin Liang0Songlin Chen1Jianzong Zhu2Xiangxue Zhou3Chen Yang4Lu Yao5Cheng Zhang6Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong ProvinceDepartment of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong ProvinceDepartment of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong ProvinceDepartment of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong ProvincePhysical examination center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, ChinaDepartment of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong ProvinceDepartment of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong ProvinceThe aim of our study was to determine the role of dystrophin hydrophobic regions in the pathogenesis of Duchenne (DMD) and Becker (BMD) muscular dystrophies, by the Kyte-Doolittle scale mean hydrophobicity profile and 3D molecular models. A total of 1038 cases diagnosed with DMD or BMD with the in-frame mutation were collected in our hospital and the Leiden DMD information database in the period 2002-2013. Correlation between clinical types and genotypes were determined on the basis of these two sources. In addition, the Kyte-Doolittle scale mean hydrophobicity of dystrophin was analyzed using BioEdit software and the models of the hydrophobic domains of dystrophin were constructed. The presence of four hydrophobic regions is confirmed. They include the calponin homology CH2 domain on the actin-binding domain (ABD), spectrin-type repeat 16, hinge III and the EF Hand domain. The severe symptoms of DMD usually develop as a result of the mutational disruption in the hydrophobic regions I, II and IV of dystrophin – those that bind associated proteins of the dystrophin-glycoprotein complex (DGC). On the other hand, when the hydrophobic region III is deleted, the connection of the ordered repeat domains of the central rod domain remains intact, resulting in the less severe clinical presentation. We conclude that mutational changes in the structure of hydrophobic regions of dystrophin play an important role in the pathogenesis of DMD. https://www.bjbms.org/ojs/index.php/bjbms/article/view/300DMDBMDdystrophinKyte-Doolittle scale mean hydrophobicity profile3D modelgenotype–phenotype analysis |
| spellingShingle | Yingyin Liang Songlin Chen Jianzong Zhu Xiangxue Zhou Chen Yang Lu Yao Cheng Zhang Dystrophin hydrophobic regions in the pathogenesis of Duchenne and Becker muscular dystrophies Biomolecules & Biomedicine DMD BMD dystrophin Kyte-Doolittle scale mean hydrophobicity profile 3D model genotype–phenotype analysis |
| title | Dystrophin hydrophobic regions in the pathogenesis of Duchenne and Becker muscular dystrophies |
| title_full | Dystrophin hydrophobic regions in the pathogenesis of Duchenne and Becker muscular dystrophies |
| title_fullStr | Dystrophin hydrophobic regions in the pathogenesis of Duchenne and Becker muscular dystrophies |
| title_full_unstemmed | Dystrophin hydrophobic regions in the pathogenesis of Duchenne and Becker muscular dystrophies |
| title_short | Dystrophin hydrophobic regions in the pathogenesis of Duchenne and Becker muscular dystrophies |
| title_sort | dystrophin hydrophobic regions in the pathogenesis of duchenne and becker muscular dystrophies |
| topic | DMD BMD dystrophin Kyte-Doolittle scale mean hydrophobicity profile 3D model genotype–phenotype analysis |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/300 |
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