7VWC

Cryo-EM structure of human very long-chain fatty acid ABC transporter ABCD1

7VWC の概要

• エントリーDOI: 10.2210/pdb7vwc/pdb
• EMDBエントリー: 32152
• 分子名称: Peroxisomal Membrane Protein related,ATP-binding cassette sub-family D member 1, [(2R)-3-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-2-oxidanyl-propyl] octadecanoate (2 entities in total)
• 機能のキーワード: very long-chain fatty, peroxisome, abc transporter, transport protein
• 由来する生物種: Caenorhabditis elegans; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 176825.21

構造登録者

Chen, Z.P.,Xu, D.,Wang, L.,Mao, Y.X.,Yang, L.,Cheng, M.T.,Hou, W.T.,Chen, Y.X.,Zhou, C.Z. (登録日: 2021-11-10, 公開日: 2022-05-18, 最終更新日: 2024-06-26)

主引用文献

Chen, Z.P.,Xu, D.,Wang, L.,Mao, Y.X.,Li, Y.,Cheng, M.T.,Zhou, C.Z.,Hou, W.T.,Chen, Y.
Structural basis of substrate recognition and translocation by human very long-chain fatty acid transporter ABCD1.
Nat Commun, 13:3299-3299, 2022

PubMed Abstract: Human ABC transporter ABCD1 transports very long-chain fatty acids from cytosol to peroxisome for β-oxidation, dysfunction of which usually causes the X-linked adrenoleukodystrophy (X-ALD). Here, we report three cryogenic electron microscopy structures of ABCD1: the apo-form, substrate- and ATP-bound forms. Distinct from what was seen in the previously reported ABC transporters, the two symmetric molecules of behenoyl coenzyme A (C22:0-CoA) cooperatively bind to the transmembrane domains (TMDs). For each C22:0-CoA, the hydrophilic 3'-phospho-ADP moiety of CoA portion inserts into one TMD, with the succeeding pantothenate and cysteamine moiety crossing the inter-domain cavity, whereas the hydrophobic fatty acyl chain extends to the opposite TMD. Structural analysis combined with biochemical assays illustrates snapshots of ABCD1-mediated substrate transport cycle. It advances our understanding on the selective oxidation of fatty acids and molecular pathology of X-ALD.

PubMed: 35676282
DOI: 10.1038/s41467-022-30974-5

実験手法

ELECTRON MICROSCOPY (3.53 Å)