View source for 8gmg


==CryoEM structure of P-Glycoprotein in Apo state==
<StructureSection load='8gmg' size='340' side='right'caption='[[8gmg]], [[Resolution|resolution]] 4.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8gmg]] 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=8GMG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GMG 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]] 4.3&#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=8gmg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gmg OCA], [https://pdbe.org/8gmg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gmg RCSB], [https://www.ebi.ac.uk/pdbsum/8gmg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gmg ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/MDR1_HUMAN MDR1_HUMAN] Ulcerative colitis. Disease susceptibility is associated with variations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/MDR1_HUMAN MDR1_HUMAN] Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
P-glycoprotein (Pgp) is an important human multidrug transporter that contributes to pharmacokinetics and multidrug resistance. Despite decades of study, the conformation transition cycle of Pgp undergoing active drug transport is not defined, thus the precise relevance of all available Pgp structures to uninterrupted multidrug transport remains unclear. Here, we use cryo-EM of membrane-embedded human Pgp under continuous turnover conditions to analyze the conformational ensembles of Pgp transporting distinct substrates. These results delineate multiple conformations including inward-facing and closed conformations, highlighting the occluded conformation as a critical intermediate state between transporter closure and substrate release. A combination of structural, functional, and computational studies reveals the transmembrane helices 4 and 10 undergoing drastic rearrangement to coordinate substrate binding, occlusion, and release, and identifies a peripheral site involved in substrate capture and Pgp inhibition. Together, our results provide a set of snapshots of Pgp undergoing continuous drug transport, unveiling the intricate interplay between transporter dynamics and drug movement, and shed light on the mechanism of polyspecificity.

Cryo-EM of human P-glycoprotein reveals an intermediate occluded conformation during active drug transport.,Culbertson AT, Liao M Nat Commun. 2025 Apr 16;16(1):3619. doi: 10.1038/s41467-025-58561-4. PMID:40240353<ref>PMID:40240353</ref>

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