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| | ==MATE transporter NorM-NG in complex with R6G and monobody== | | ==MATE transporter NorM-NG in complex with R6G and monobody== |
| - | <StructureSection load='4hun' size='340' side='right' caption='[[4hun]], [[Resolution|resolution]] 3.59Å' scene=''> | + | <StructureSection load='4hun' size='340' side='right'caption='[[4hun]], [[Resolution|resolution]] 3.59Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hun]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895] and [http://en.wikipedia.org/wiki/Neisseria_gonorrhoeae_tcdc-ng08107 Neisseria gonorrhoeae tcdc-ng08107]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HUN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HUN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hun]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Neisseria_gonorrhoeae_TCDC-NG08107 Neisseria gonorrhoeae TCDC-NG08107]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HUN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HUN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RHQ:RHODAMINE+6G'>RHQ</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.59Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4huk|4huk]], [[4hul|4hul]], [[4hum|4hum]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RHQ:RHODAMINE+6G'>RHQ</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NGTW08_0430 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=940296 Neisseria gonorrhoeae TCDC-NG08107])</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=4hun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hun OCA], [https://pdbe.org/4hun PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hun RCSB], [https://www.ebi.ac.uk/pdbsum/4hun PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hun ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hun OCA], [http://pdbe.org/4hun PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hun RCSB], [http://www.ebi.ac.uk/pdbsum/4hun PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hun ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/M1E1G6_ECOLX M1E1G6_ECOLX] |
| - | Multidrug transporters belonging to the multidrug and toxic compound extrusion (MATE) family expel dissimilar lipophilic and cationic drugs across cell membranes by dissipating a preexisting Na(+) or H(+) gradient. Despite its clinical relevance, the transport mechanism of MATE proteins remains poorly understood, largely owing to a lack of structural information on the substrate-bound transporter. Here we report crystal structures of a Na(+)-coupled MATE transporter NorM from Neisseria gonorrheae in complexes with three distinct translocation substrates (ethidium, rhodamine 6G, and tetraphenylphosphonium), as well as Cs(+) (a Na(+) congener), all captured in extracellular-facing and drug-bound states. The structures revealed a multidrug-binding cavity festooned with four negatively charged amino acids and surprisingly limited hydrophobic moieties, in stark contrast to the general belief that aromatic amino acids play a prominent role in multidrug recognition. Furthermore, we discovered an uncommon cation-pi interaction in the Na(+)-binding site located outside the drug-binding cavity and validated the biological relevance of both the substrate- and cation-binding sites by conducting drug resistance and transport assays. Additionally, we uncovered potential rearrangement of at least two transmembrane helices upon Na(+)-induced drug export. Based on our structural and functional analyses, we suggest that Na(+) triggers multidrug extrusion by inducing protein conformational changes rather than by directly competing for the substrate-binding amino acids. This scenario is distinct from the canonical antiport mechanism, in which both substrate and counterion compete for a shared binding site in the transporter. Collectively, our findings provide an important step toward a detailed and mechanistic understanding of multidrug transport.
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| - | Structures of a Na+-coupled, substrate-bound MATE multidrug transporter.,Lu M, Symersky J, Radchenko M, Koide A, Guo Y, Nie R, Koide S Proc Natl Acad Sci U S A. 2013 Jan 22. PMID:23341609<ref>PMID:23341609</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 4hun" style="background-color:#fffaf0;"></div>
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| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| - | [[Category: Neisseria gonorrhoeae tcdc-ng08107]] | + | [[Category: Large Structures]] |
| - | [[Category: Lu, M]] | + | [[Category: Neisseria gonorrhoeae TCDC-NG08107]] |
| - | [[Category: Transport protein]] | + | [[Category: Lu M]] |
