8jw4: Difference between revisions

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-'''Unreleased structure'''
-The entry 8jw4 is ON HOLD
+==Cryo-EM structure of Plasmodium falciparum multidrug resistance protein 1 in the apo state without H1 helix==
+<StructureSection load='8jw4' size='340' side='right'caption='[[8jw4]], [[Resolution|resolution]] 3.13&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8jw4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8JW4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JW4 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]] 3.13&#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=8jw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jw4 OCA], [https://pdbe.org/8jw4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jw4 RCSB], [https://www.ebi.ac.uk/pdbsum/8jw4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jw4 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q7K6A5_PLAF7 Q7K6A5_PLAF7]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Plasmodium falciparum multidrug resistance protein 1 (PfMDR1), an adenosine triphosphate (ATP)-binding cassette (ABC) transporter on the digestive vacuole (DV) membrane of the parasite, is associated with the resistance to antimalarial drugs. To understand the mechanisms of PfMDR1, we determined the cryo-electron microscopy structures of this transporter in different states. The transporter in the apo state shows an inward-facing conformation with a large cavity opening to the cytoplasm. Upon ATP binding and dimerization of the nucleotide-binding domains (NBDs), PfMDR1 displays an outward-facing conformation with a cavity toward the DV lumen. Drug resistance-associated mutations were investigated in both structures for their effects, and Y184F was identified as an allosteric activity-enhancing mutation. The amphiphilic substrate-binding site of PfMDR1 was revealed by the complex structure with the antimalarial drug mefloquine and confirmed by mutagenesis studies. Remarkably, a helical structure was found to hinder NBD dimerization and inhibit PfMDR1 activity. The location of this regulatory domain in the N terminus is different from the well-studied R domain in the internal linker region of other ABC transporter family members. The lack of the phosphorylation site of this domain also suggests a different regulation mechanism.
-Authors: Li, M., Si, K.
+The structure of Plasmodium falciparum multidrug resistance protein 1 reveals an N-terminal regulatory domain.,Si K, He X, Chen L, Zhang A, Guo C, Li M Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2219905120. doi: , 10.1073/pnas.2219905120. Epub 2023 Aug 1. PMID:37527341<ref>PMID:37527341</ref>
-Description: Cryo-EM structure of Plasmodium falciparum multidrug resistance protein 1 in the apo state without H1 helix
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Li, M]]
+<div class="pdbe-citations 8jw4" style="background-color:#fffaf0;"></div>
-[[Category: Si, K]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Plasmodium falciparum 3D7]]
+[[Category: Li M]]
+[[Category: Si K]]