View source for 7niu


==Nanodisc reconstituted human ABCB4 in complex with 4B1-Fab and QA2-Fab (apo-inward-open conformation)==
<StructureSection load='7niu' size='340' side='right'caption='[[7niu]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7niu]] is a 5 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=7NIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NIU 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]] 4.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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=7niu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7niu OCA], [https://pdbe.org/7niu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7niu RCSB], [https://www.ebi.ac.uk/pdbsum/7niu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7niu ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ABCB4 is expressed in hepatocytes and translocates phosphatidylcholine into bile canaliculi. The mechanism of specific lipid recruitment from the canalicular membrane, which is essential to mitigate the cytotoxicity of bile salts, is poorly understood. We present cryogenic electron microscopy structures of human ABCB4 in three distinct functional conformations. An apo-inward structure reveals how phospholipid can be recruited from the inner leaflet of the membrane without flipping its orientation. An occluded structure reveals a single phospholipid molecule in a central cavity. Its choline moiety is stabilized by cation-pi interactions with an essential tryptophan residue, rationalizing the specificity of ABCB4 for phosphatidylcholine. In an inhibitor-bound structure, a posaconazole molecule blocks phospholipids from reaching the central cavity. Using a proteoliposome-based translocation assay with fluorescently labeled phosphatidylcholine analogs, we recapitulated the substrate specificity of ABCB4 in vitro and confirmed the role of the key tryptophan residue. Our results provide a structural basis for understanding an essential translocation step in the generation of bile and its sensitivity to azole drugs.

Structures of ABCB4 provide insight into phosphatidylcholine translocation.,Nosol K, Bang-Sorensen R, Irobalieva RN, Erramilli SK, Stieger B, Kossiakoff AA, Locher KP Proc Natl Acad Sci U S A. 2021 Aug 17;118(33):e2106702118. doi: , 10.1073/pnas.2106702118. PMID:34385322<ref>PMID:34385322</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7niu" style="background-color:#fffaf0;"></div>

==See Also==
*[[ABC transporter 3D structures|ABC transporter 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Locher KP]]
[[Category: Nosol K]]