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-Structure paper
タイトル | Structural and functional insights of the human peroxisomal ABC transporter ALDP. |
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ジャーナル・号・ページ | Elife, Vol. 11, Year 2022 |
掲載日 | 2022年11月14日 |
著者 | Yutian Jia / Yanming Zhang / Wenhao Wang / Jianlin Lei / Zhengxin Ying / Guanghui Yang / |
PubMed 要旨 | Adrenoleukodystrophy protein (ALDP) is responsible for the transport of very-long-chain fatty acids (VLCFAs) and corresponding CoA-esters across the peroxisomal membrane. Dysfunction of ALDP leads to ...Adrenoleukodystrophy protein (ALDP) is responsible for the transport of very-long-chain fatty acids (VLCFAs) and corresponding CoA-esters across the peroxisomal membrane. Dysfunction of ALDP leads to peroxisomal metabolic disorder exemplified by X-linked adrenoleukodystrophy (ALD). Hundreds of ALD-causing mutations have been identified on ALDP. However, the pathogenic mechanisms of these mutations are restricted to clinical description due to limited structural and biochemical characterization. Here we report the cryo-electron microscopy structure of human ALDP with nominal resolution at 3.4 Å. ALDP exhibits a cytosolic-facing conformation. Compared to other lipid ATP-binding cassette transporters, ALDP has two substrate binding cavities formed by the transmembrane domains. Such structural organization may be suitable for the coordination of VLCFAs. Based on the structure, we performed integrative analysis of the cellular trafficking, protein thermostability, ATP hydrolysis, and the transport activity of representative mutations. These results provide a framework for understanding the working mechanism of ALDP and pathogenic roles of disease-associated mutations. |
リンク | Elife / PubMed:36374178 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.4 Å |
構造データ | EMDB-32096, PDB-7vr1: |
由来 |
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キーワード | TRANSLOCASE / Membrane protein / LIPID TRANSPORT |