دورية أكاديمية
Structural insights into substrate recognition and translocation of human peroxisomal ABC transporter ALDP
| العنوان: | Structural insights into substrate recognition and translocation of human peroxisomal ABC transporter ALDP |
|---|---|
| المؤلفون: | Chao Xiong, Li-Na Jia, Wei-Xi Xiong, Xin-Tong Wu, Liu-Lin Xiong, Ting-Hua Wang, Dong Zhou, Zhen Hong, Zheng Liu, Lin Tang |
| المصدر: | Signal Transduction and Targeted Therapy, Vol 8, Iss 1, Pp 1-13 (2023) |
| بيانات النشر: | Nature Publishing Group, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine LCC:Biology (General) |
| مصطلحات موضوعية: | Medicine, Biology (General), QH301-705.5 |
| الوصف: | Abstract Dysfunctions of ATP-binding cassette, subfamily D, member 1 (ABCD1) cause X-linked adrenoleukodystrophy, a rare neurodegenerative disease that affects all human tissues. Residing in the peroxisome membrane, ABCD1 plays a role in the translocation of very long-chain fatty acids for their β-oxidation. Here, the six cryo-electron microscopy structures of ABCD1 in four distinct conformational states were presented. In the transporter dimer, two transmembrane domains form the substrate translocation pathway, and two nucleotide-binding domains form the ATP-binding site that binds and hydrolyzes ATP. The ABCD1 structures provide a starting point for elucidating the substrate recognition and translocation mechanism of ABCD1. Each of the four inward-facing structures of ABCD1 has a vestibule that opens to the cytosol with variable sizes. Hexacosanoic acid (C26:0)-CoA substrate binds to the transmembrane domains (TMDs) and stimulates the ATPase activity of the nucleotide-binding domains (NBDs). W339 from the transmembrane helix 5 (TM5) is essential for binding substrate and stimulating ATP hydrolysis by substrate. ABCD1 has a unique C-terminal coiled-coil domain that negatively modulates the ATPase activity of the NBDs. Furthermore, the structure of ABCD1 in the outward-facing state indicates that ATP molecules pull the two NBDs together and open the TMDs to the peroxisomal lumen for substrate release. The five structures provide a view of the substrate transport cycle and mechanistic implication for disease-causing mutations. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2059-3635 |
| Relation: | https://doaj.org/toc/2059-3635 |
| DOI: | 10.1038/s41392-022-01280-9 |
| URL الوصول: | https://doaj.org/article/cac389f9c9164401a54170180c4ddefb |
| رقم الأكسشن: | edsdoj.389f9c9164401a54170180c4ddefb |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20593635 |
|---|---|
| DOI: | 10.1038/s41392-022-01280-9 |