4hul: Difference between revisions

Line 1:

[[~~Image~~:~~4hul~~.~~png~~|~~left~~|~~200px~~]]

==MATE transporter NorM-NG in complex with Cs+ and monobody==

== Structural highlights ==

<table><tr><td colspan='2'>[[4hul]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] 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=4HUL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HUL FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CS:CESIUM+ION'>CS</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4huk|4huk]], [[4hum|4hum]], [[4hun|4hun]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hul OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hul RCSB], [http://www.ebi.ac.uk/pdbsum/4hul PDBsum]</span></td></tr>

</table>

== Publication Abstract from PubMed ==

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.

~~{{STRUCTURE_4hul| PDB=4hul | SCENE= }}~~

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>

~~===MATE transporter NorM-NG in complex with Cs+ and monobody===~~

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

</div>

~~{{ABSTRACT_PUBMED_23341609}}~~

== References ==

==~~About this Structure~~==

__TOC__

~~[[4hul]] is a 2 chain structure with sequence from [http:~~//en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] 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=4HUL OCA].

</StructureSection>

[[Category: Escherichia coli]]

[[Category: Neisseria gonorrhoeae tcdc-ng08107]]

[[Category: Lu, M.]]

[[Category: Lu, M]]

[[Category: Transport protein]]

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@@ Line 1: / Line 1: @@
-[[Image:4hul.png|left|200px]]
+==MATE transporter NorM-NG in complex with Cs+ and monobody==
+<StructureSection load='4hul' size='340' side='right' caption='[[4hul]], [[Resolution|resolution]] 3.81&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4hul]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] 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=4HUL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HUL FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CS:CESIUM+ION'>CS</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4huk|4huk]], [[4hum|4hum]], [[4hun|4hun]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hul OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hul RCSB], [http://www.ebi.ac.uk/pdbsum/4hul PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-{{STRUCTURE_4hul|  PDB=4hul  |  SCENE=  }}
+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>
-===MATE transporter NorM-NG in complex with Cs+ and monobody===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_23341609}}
+== References ==
+<references/>
-==About this Structure==
+__TOC__
-[[4hul]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] 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=4HUL OCA].
+</StructureSection>
 [[Category: Escherichia coli]]
 [[Category: Neisseria gonorrhoeae tcdc-ng08107]]
-[[Category: Lu, M.]]
+[[Category: Lu, M]]
 [[Category: Transport protein]]