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Title | Structural basis of substrate recognition and translocation by human very long-chain fatty acid transporter ABCD1. |
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Journal, issue, pages | Nat Commun, Vol. 13, Issue 1, Page 3299, Year 2022 |
Publish date | Jun 8, 2022 |
Authors | Zhi-Peng Chen / Da Xu / Liang Wang / Yao-Xu Mao / Yang Li / Meng-Ting Cheng / Cong-Zhao Zhou / Wen-Tao Hou / Yuxing Chen / |
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 ...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. |
External links | Nat Commun / PubMed:35676282 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.8 - 3.59 Å |
Structure data | EMDB-32152, PDB-7vwc: EMDB-32171, PDB-7vx8: EMDB-32224, PDB-7vzb: |
Chemicals | ChemComp-82T: ChemComp-ATP: ChemComp-MG: ChemComp-Y01: ChemComp-FFI: |
Source |
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Keywords | TRANSPORT PROTEIN / very long-chain fatty / Peroxisome / ABC transporter |