View source for 7tdt


==Cryo-EM structure of nanodisc-embedded human ABCA1==
<StructureSection load='7tdt' size='340' side='right'caption='[[7tdt]], [[Resolution|resolution]] 4.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7tdt]] 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=7TDT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TDT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4&#8491;</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=7tdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tdt OCA], [https://pdbe.org/7tdt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tdt RCSB], [https://www.ebi.ac.uk/pdbsum/7tdt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tdt ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ABCA1_HUMAN ABCA1_HUMAN] Tangier disease;Apolipoprotein A-I deficiency. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/ABCA1_HUMAN ABCA1_HUMAN] cAMP-dependent and sulfonylurea-sensitive anion transporter. Key gatekeeper influencing intracellular cholesterol transport.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The human ATP-binding cassette (ABC) transporter ABCA1 plays a critical role in lipid homeostasis as it extracts sterols and phospholipids from the plasma membrane for excretion to the extracellular apolipoprotein A-I and subsequent formation of high-density lipoprotein (HDL) particles. Deleterious mutations of ABCA1 lead to sterol accumulation and are associated with atherosclerosis, poor cardiovascular outcomes, cancer, and Alzheimer's disease. The mechanism by which ABCA1 drives lipid movement is poorly understood, and a unified platform to produce active ABCA1 protein for both functional and structural studies has been missing. In this work, we established a stable expression system for both a human cell-based sterol export assay and protein purification for in vitro biochemical and structural studies. ABCA1 produced in this system was active in sterol export and displayed enhanced ATPase activity after reconstitution into a lipid bilayer. Our single-particle cryo-EM study of ABCA1 in nanodiscs showed protein induced membrane curvature, revealed multiple distinct conformations, and generated a structure of nanodisc-embedded ABCA1 at 4.0-A resolution representing a previously unknown conformation. Comparison of different ABCA1 structures and molecular dynamics simulations demonstrates both concerted domain movements and conformational variations within each domain. Taken together, our platform for producing and characterizing ABCA1 in a lipid membrane enabled us to gain important mechanistic and structural insights and paves the way for investigating modulators that target the functions of ABCA1.

Activity and Structural Dynamics of Human ABCA1 in a Lipid Membrane.,Plummer-Medeiros AM, Culbertson AT, Morales-Perez CL, Liao M J Mol Biol. 2023 Apr 15;435(8):168038. doi: 10.1016/j.jmb.2023.168038. Epub 2023 , Mar 7. PMID:36889459<ref>PMID:36889459</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7tdt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Culbertson AT]]
[[Category: Liao M]]
[[Category: Morales-Perez CL]]
[[Category: Plummer AM]]