View source for 7xec


==Cryo-EM structure of human ABCD1 E630Q in the presence of ATP in inward-facing state 2==
<StructureSection load='7xec' size='340' side='right'caption='[[7xec]], [[Resolution|resolution]] 3.34&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7xec]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XEC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7xec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xec OCA], [https://pdbe.org/7xec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xec RCSB], [https://www.ebi.ac.uk/pdbsum/7xec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xec ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Dysfunctions of ATP-binding cassette, subfamily D, member 1 (ABCD1) cause X-linked adrenoleukodystrophy, a rare neurodegenerative disease that affects all human tissues. Residing in the peroxisome membrane, ABCD1 plays a role in the translocation of very long-chain fatty acids for their beta-oxidation. Here, the six cryo-electron microscopy structures of ABCD1 in four distinct conformational states were presented. In the transporter dimer, two transmembrane domains form the substrate translocation pathway, and two nucleotide-binding domains form the ATP-binding site that binds and hydrolyzes ATP. The ABCD1 structures provide a starting point for elucidating the substrate recognition and translocation mechanism of ABCD1. Each of the four inward-facing structures of ABCD1 has a vestibule that opens to the cytosol with variable sizes. Hexacosanoic acid (C26:0)-CoA substrate binds to the transmembrane domains (TMDs) and stimulates the ATPase activity of the nucleotide-binding domains (NBDs). W339 from the transmembrane helix 5 (TM5) is essential for binding substrate and stimulating ATP hydrolysis by substrate. ABCD1 has a unique C-terminal coiled-coil domain that negatively modulates the ATPase activity of the NBDs. Furthermore, the structure of ABCD1 in the outward-facing state indicates that ATP molecules pull the two NBDs together and open the TMDs to the peroxisomal lumen for substrate release. The five structures provide a view of the substrate transport cycle and mechanistic implication for disease-causing mutations.

Structural insights into substrate recognition and translocation of human peroxisomal ABC transporter ALDP.,Xiong C, Jia LN, Xiong WX, Wu XT, Xiong LL, Wang TH, Zhou D, Hong Z, Liu Z, Tang L Signal Transduct Target Ther. 2023 Feb 22;8(1):74. doi: , 10.1038/s41392-022-01280-9. PMID:36810450<ref>PMID:36810450</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7xec" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chao X]]
[[Category: Li-Na J]]
[[Category: Lin T]]