دورية أكاديمية
Structural bioinformatics studies of six human ABC transporters and their AlphaFold2-predicted water-soluble QTY variants
| العنوان: | Structural bioinformatics studies of six human ABC transporters and their AlphaFold2-predicted water-soluble QTY variants |
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| المؤلفون: | Emily Pan, Fei Tao, Eva Smorodina, Shuguang Zhang |
| المصدر: | QRB Discovery, Vol 5 (2024) |
| بيانات النشر: | Cambridge University Press, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Biotechnology LCC:Biology (General) |
| مصطلحات موضوعية: | convert hydrophobic alpha helix to hydrophilic alpha helix, membrane protein design, protein structural predictions, QTY code, water-soluble integral membrane proteins, Biotechnology, TP248.13-248.65, Biology (General), QH301-705.5 |
| الوصف: | Human ATP-binding cassette (ABC) transporters are one of the largest families of membrane proteins and perform diverse functions. Many of them are associated with multidrug resistance that often results in cancer treatment with poor outcomes. Here, we present the structural bioinformatics study of six human ABC membrane transporters with experimentally determined cryo-electron microscopy (CryoEM) structures including ABCB7, ABCC8, ABCD1, ABCD4, ABCG1, ABCG5, and their AlphaFold2-predicted water-soluble QTY variants. In the native structures, there are hydrophobic amino acids such as leucine (L), isoleucine (I), valine (V), and phenylalanine (F) in the transmembrane alpha helices. These hydrophobic amino acids are systematically replaced by hydrophilic amino acids glutamine (Q), threonine (T), and tyrosine (Y). Therefore, these QTY variants become water soluble. We also present the superposed structures of native ABC transporters and their water-soluble QTY variants. The superposed structures show remarkable similarity with root mean square deviations between 1.064 and 3.413 Å despite significant (41.90–54.33%) changes to the protein sequence of the transmembrane domains. We also show the differences in hydrophobicity patches between the native ABC transporters and their QTY variants. We explain the rationale behind why the QTY membrane protein variants become water soluble. Our structural bioinformatics studies provide insight into the differences between the hydrophobic helices and hydrophilic helices and will likely further stimulate designs of water-soluble multispan transmembrane proteins and other aggregated proteins. The water-soluble ABC transporters may be useful as soluble antigens to generate therapeutic monoclonal antibodies for combating multidrug resistance in clinics. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2633-2892 |
| Relation: | https://www.cambridge.org/core/product/identifier/S2633289224000024/type/journal_article; https://doaj.org/toc/2633-2892 |
| DOI: | 10.1017/qrd.2024.2 |
| URL الوصول: | https://doaj.org/article/52e885aef2ec4996bad45e082b5bfb27 |
| رقم الأكسشن: | edsdoj.52e885aef2ec4996bad45e082b5bfb27 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 26332892 |
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| DOI: | 10.1017/qrd.2024.2 |