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-Structure paper
タイトル | Structures of the human peroxisomal fatty acid transporter ABCD1 in a lipid environment. |
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ジャーナル・号・ページ | Commun Biol, Vol. 5, Issue 1, Page 7, Year 2022 |
掲載日 | 2022年1月10日 |
著者 | Le Thi My Le / James Robert Thompson / Phuoc Xuan Dang / Janarjan Bhandari / Amer Alam / |
PubMed 要旨 | The peroxisomal very long chain fatty acid (VLCFA) transporter ABCD1 is central to fatty acid catabolism and lipid biosynthesis. Its dysfunction underlies toxic cytosolic accumulation of VLCFAs, ...The peroxisomal very long chain fatty acid (VLCFA) transporter ABCD1 is central to fatty acid catabolism and lipid biosynthesis. Its dysfunction underlies toxic cytosolic accumulation of VLCFAs, progressive demyelination, and neurological impairments including X-linked adrenoleukodystrophy (X-ALD). We present cryo-EM structures of ABCD1 in phospholipid nanodiscs in a nucleotide bound conformation open to the peroxisomal lumen and an inward facing conformation open to the cytosol at up to 3.5 Å resolution, revealing details of its transmembrane cavity and ATP dependent conformational spectrum. We identify features distinguishing ABCD1 from its closest homologs and show that coenzyme A (CoA) esters of VLCFAs modulate ABCD1 activity in a species dependent manner. Our data suggest a transport mechanism where the CoA moieties of VLCFA-CoAs enter the hydrophilic transmembrane domain while the acyl chains extend out into the surrounding membrane bilayer. The structures help rationalize disease causing mutations and may aid ABCD1 targeted structure-based drug design. |
リンク | Commun Biol / PubMed:35013584 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.5 - 4.4 Å |
構造データ | EMDB-24656, PDB-7rr9: EMDB-24657, PDB-7rra: |
化合物 |
ChemComp-UNL: ChemComp-CLR: ChemComp-MG: ChemComp-AGS: |
由来 |
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キーワード | TRANSPORT PROTEIN / VLCFA ABC transporter ABCD1 |