7VZB

Cryo-EM structure of C22:0-CoA bound human very long-chain fatty acid ABC transporter ABCD1

Summary for 7VZB

• Entry DOI: 10.2210/pdb7vzb/pdb
• EMDB information: 32224
• Descriptor: Peroxisomal Membrane Protein related,ATP-binding cassette sub-family D member 1, CHOLESTEROL HEMISUCCINATE, S-[2-[3-[[(2R)-4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-oxidanyl-3-phosphonooxy-oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-oxidanyl-phosphoryl]oxy-3,3-dimethyl-2-oxidanyl-butanoyl]amino]propanoylamino]ethyl] docosanethioate (3 entities in total)
• Functional Keywords: very long-chain fatty, peroxisome, abc transporter, transport protein
• Biological source: Caenorhabditis elegans; More
• Total number of polymer chains: 2
• Total formula weight: 179015.66

Authors

Chen, Z.P.,Xu, D.,Wang, L.,Mao, Y.X.,Yang, L.,Cheng, M.T.,Hou, W.T.,Chen, Y.X.,Zhou, C.Z. (deposition date: 2021-11-15, release date: 2022-05-18, Last modification date: 2024-06-26)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.59 Å)