View source for 8eop


==Cryo-EM Structure of Nanodisc reconstituted human ABCA7 EQ mutant in ATP bound closed state==
<StructureSection load='8eop' size='340' side='right'caption='[[8eop]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8eop]] is a 1 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=8EOP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EOP 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>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=8eop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8eop OCA], [https://pdbe.org/8eop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8eop RCSB], [https://www.ebi.ac.uk/pdbsum/8eop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8eop ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ABCA7_HUMAN ABCA7_HUMAN] Early-onset autosomal dominant Alzheimer disease;NON RARE IN EUROPE: Alzheimer disease. Disease susceptibility is associated with variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/ABCA7_HUMAN ABCA7_HUMAN] Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981). Transports preferentially phosphatidylserine over phosphatidylcholine (PubMed:24097981). Plays a role in lipid homeostasis and macrophage-mediated phagocytosis (PubMed:14592415, PubMed:12917409, PubMed:12925201, PubMed:14570867). Binds APOA1 and may function in apolipoprotein-mediated phospholipid efflux from cells (PubMed:12917409, PubMed:14570867, PubMed:14592415). May also mediate cholesterol efflux (PubMed:14570867). May regulate cellular ceramide homeostasis during keratinocyte differentiation (PubMed:12925201). Involved in lipid raft organization and CD1D localization on thymocytes and antigen-presenting cells, which plays an important role in natural killer T-cell development and activation (By similarity). Plays a role in phagocytosis of apoptotic cells by macrophages (By similarity). Macrophage phagocytosis is stimulated by APOA1 or APOA2, probably by stabilization of ABCA7 (By similarity). Also involved in phagocytic clearance of amyloid-beta by microglia cells and macrophages (By similarity). Further limits amyloid-beta production by playing a role in the regulation of amyloid-beta A4 precursor protein (APP) endocytosis and/or processing (PubMed:26260791). Amyloid-beta is the main component of amyloid plaques found in the brains of Alzheimer patients (PubMed:26260791).[UniProtKB:Q91V24]<ref>PMID:12917409</ref> <ref>PMID:12925201</ref> <ref>PMID:14570867</ref> <ref>PMID:14592415</ref> <ref>PMID:24097981</ref> <ref>PMID:26260791</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Phospholipid extrusion by ABC subfamily A (ABCA) exporters is central to cellular physiology, although the specifics of the underlying substrate interactions and transport mechanisms remain poorly resolved at the molecular level. Here we report cryo-EM structures of lipid-embedded human ABCA7 in an open state and in a nucleotide-bound, closed state at resolutions between 3.6 and 4.0 A. The former reveals an ordered patch of bilayer lipids traversing the transmembrane domain (TMD), while the latter reveals a lipid-free, closed TMD with a small extracellular opening. These structures offer a structural framework for both substrate entry and exit from the ABCA7 TMD and highlight conserved rigid-body motions that underlie the associated conformational transitions. Combined with functional analysis and molecular dynamics (MD) simulations, our data also shed light on lipid partitioning into the ABCA7 TMD and localized membrane perturbations that underlie ABCA7 function and have broader implications for other ABCA family transporters.

Cryo-EM structures of human ABCA7 provide insights into its phospholipid translocation mechanisms.,Le LTM, Thompson JR, Dehghani-Ghahnaviyeh S, Pant S, Dang PX, French JB, Kanikeyo T, Tajkhorshid E, Alam A EMBO J. 2022 Dec 9:e111065. doi: 10.15252/embj.2022111065. PMID:36484366<ref>PMID:36484366</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8eop" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Alam A]]
[[Category: Le LTM]]
[[Category: Thompson JR]]