5ofr - Revision history

OCA at 16:48, 13 December 2023

OCA — Wed, 13 Dec 2023 16:48:27 GMT

←Older revision		Revision as of 16:48, 13 December 2023
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	==Structure of the antibacterial peptide ABC transporter McjD in a high energy outward occluded intermediate state==		==Structure of the antibacterial peptide ABC transporter McjD in a high energy outward occluded intermediate state==
-	<StructureSection load='5ofr' size='340' side='right' caption='[[5ofr]], [[Resolution\|resolution]] 3.40Å' scene=''>	+	<StructureSection load='5ofr' size='340' side='right'caption='[[5ofr]], [[Resolution\|resolution]] 3.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ofr]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"bacillus_coli"_migula_1895 "bacillus~~ coli~~" migula 1895~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OFR OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5OFR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ofr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OFR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OFR FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VO4:VANADATE+ION'>VO4</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]] 3.4Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">mcjD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VO4:VANADATE+ION'>VO4</scene></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=5ofr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ofr OCA], [~~http~~://pdbe.org/5ofr PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5ofr RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5ofr PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5ofr ProSAT]</span></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=5ofr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ofr OCA], [https://pdbe.org/5ofr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ofr RCSB], [https://www.ebi.ac.uk/pdbsum/5ofr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ofr ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MCJD_ECOLX MCJD_ECOLX]] Is able to protect a cell, which harbors the plasmid pTUC100 encoding microcin J25, against microcin J25. Is required for microcin J25 export out of the producing cells.<ref>PMID:10198038</ref> <ref>PMID:8655570</ref>	+	[https://www.uniprot.org/uniprot/MCJD_ECOLX MCJD_ECOLX] Is able to protect a cell, which harbors the plasmid pTUC100 encoding microcin J25, against microcin J25. Is required for microcin J25 export out of the producing cells.<ref>PMID:10198038</ref> <ref>PMID:8655570</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bacillus~~ coli ~~migula 1895~~]]	+	[[Category: Escherichia coli]]
-	[[Category: ~~Beis, K~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Bountra,~~ K]]	+	[[Category: Beis K]]
-	[[Category: ~~Abc transporter]]~~	+	[[Category: Bountra K]]
-	~~[[Category: Adp-vo4]]~~	+
-	~~[[Category: Antibacterial peptide]]~~	+
-	~~[[Category: High energy outward occluded intermediate]]~~	+
-	~~[[Category: Membrane protein~~]]	+

OCA at 10:09, 22 November 2017

OCA — Wed, 22 Nov 2017 10:09:36 GMT

←Older revision		Revision as of 10:09, 22 November 2017
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	<StructureSection load='5ofr' size='340' side='right' caption='[[5ofr]], [[Resolution\|resolution]] 3.40Å' scene=''>		<StructureSection load='5ofr' size='340' side='right' caption='[[5ofr]], [[Resolution\|resolution]] 3.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ofr]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OFR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OFR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ofr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OFR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OFR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VO4:VANADATE+ION'>VO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VO4:VANADATE+ION'>VO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">mcjD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=5ofr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ofr OCA], [http://pdbe.org/5ofr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ofr RCSB], [http://www.ebi.ac.uk/pdbsum/5ofr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ofr 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=5ofr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ofr OCA], [http://pdbe.org/5ofr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ofr RCSB], [http://www.ebi.ac.uk/pdbsum/5ofr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ofr ProSAT]</span></td></tr>
	</table>		</table>
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	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~Enterobacteriaceae~~ produce ~~antimicrobial~~ peptides ~~for survival under~~ nutrient ~~starvation~~. ~~Microcin J25 (MccJ25) is an antimicrobial peptide with a unique lasso topology. It is secreted by~~ the ~~ATP-binding cassette (~~ABC~~) exporter McjD, which ensures~~ self-immunity of the ~~producing strain through efficient export of the toxic mature~~ peptide ~~from the cell. Here we have~~ determined ~~the crystal structure of~~ McjD ~~from Escherichia coli at 2.7-A resolution, which is to the authors' knowledge the first~~ structure ~~of an~~ antibacterial peptide ~~ABC transporter. Our functional and biochemical analyses demonstrate McjD-dependent immunity to MccJ25 through~~ efflux ~~of the peptide~~. ~~McjD can directly bind MccJ25 and displays~~ a ~~basal ATPase activity that is stimulated by MccJ25 in both detergent solution~~ and ~~proteoliposomes. McjD adopts~~ a new ~~conformation, termed~~ nucleotide-bound ~~outward occluded. The new conformation defines a clear cavity; mutagenesis and ligand binding studies of the cavity have identified Phe86~~, ~~Asn134, and Asn302 as important for recognition of MccJ25. Comparisons with the inward~~-~~open MsbA and~~ outward-~~open Sav1866 structures show that McjD has structural similarities with both states without the intertwining of transmembrane (TM) helices. The~~ occluded state ~~is formed by rotation of TMs 1 and 2 toward the equivalent TMs of the opposite monomer~~, ~~unlike Sav1866 where they intertwine~~ with ~~TMs 3-6 of the opposite monomer~~. ~~Cysteine~~ cross-linking ~~studies on the McjD dimer~~ in ~~inside-out membrane vesicles of~~ E. coli ~~confirmed~~ the ~~presence~~ of the ~~occluded state~~. We ~~therefore~~ propose that the ~~outward-occluded state represents a transition intermediate between~~ the ~~outward~~-~~open and inward~~-~~open conformation of ABC exporters~~.	+	Certain pathogenic bacteria produce and release toxic peptides to ensure either nutrient availability or evasion from the immune system. These peptides are also toxic to the producing bacteria that utilize dedicated ABC transporters to provide self-immunity. The ABC transporter McjD exports the antibacterial peptide MccJ25 in Escherichia coli Our previously determined McjD structure provided some mechanistic insights into antibacterial peptide efflux. In this study, we have determined its structure in a novel conformation, apo inward-occluded and a new nucleotide-bound state, high-energy outward-occluded intermediate state, with a defined ligand binding cavity. Predictive cysteine cross-linking in E. coli membranes and PELDOR measurements along the transport cycle indicate that McjD does not undergo major conformational changes as previously proposed for multi-drug ABC exporters. Combined with transport assays and molecular dynamics simulations, we propose a novel mechanism for toxic peptide ABC exporters that only requires the transient opening of the cavity for release of the peptide. We propose that shielding of the cavity ensures that the transporter is available to export the newly synthesized peptides, preventing toxic-level build-up.

-	~~Structure of an~~ antibacterial peptide ~~ATP~~-~~binding cassette~~ transporter ~~in a novel outward occluded state~~.,Choudhury HG, ~~Tong Z~~, Mathavan I~~, Li Y, Iwata S~~, Zirah S, Rebuffat S~~, van Veen HW~~, Beis K ~~Proc Natl Acad Sci U S A~~. ~~2014 Jun 11~~. ~~pii~~: ~~201320506~~. PMID:~~24920594~~<ref>PMID:~~24920594~~</ref>	+	Structural basis for antibacterial peptide self-immunity by the bacterial ABC transporter McjD.,Bountra K, Hagelueken G, Choudhury HG, Corradi V, El Omari K, Wagner A, Mathavan I, Zirah S, Yuan Wahlgren W, Tieleman DP, Schiemann O, Rebuffat S, Beis K EMBO J. 2017 Oct 16;36(20):3062-3079. doi: 10.15252/embj.201797278. Epub 2017 Sep, 1. PMID:28864543<ref>PMID:28864543</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bacillus coli migula 1895]]
	[[Category: Beis, K]]		[[Category: Beis, K]]
	[[Category: Bountra, K]]		[[Category: Bountra, K]]

OCA: Protected "5ofr" [edit=sysop:move=sysop]

OCA — Wed, 13 Sep 2017 09:45:00 GMT

Protected "5ofr" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:45, 13 September 2017

OCA: New page: ==Structure of the antibacterial peptide ABC transporter McjD in a high energy outward occluded intermediate state== == Structural highlights ==
<table><tr><td colspan='2'>[[5ofr]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OFR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OFR FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VO4:VANADATE+ION'>VO4</scene></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=5ofr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ofr OCA], [http://pdbe.org/5ofr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ofr RCSB], [http://www.ebi.ac.uk/pdbsum/5ofr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ofr ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/MCJD_ECOLX MCJD_ECOLX]] Is able to protect a cell, which harbors the plasmid pTUC100 encoding microcin J25, against microcin J25. Is required for microcin J25 export out of the producing cells.<ref>PMID:10198038</ref> <ref>PMID:8655570</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Enterobacteriaceae produce antimicrobial peptides for survival under nutrient starvation. Microcin J25 (MccJ25) is an antimicrobial peptide with a unique lasso topology. It is secreted by the ATP-binding cassette (ABC) exporter McjD, which ensures self-immunity of the producing strain through efficient export of the toxic mature peptide from the cell. Here we have determined the crystal structure of McjD from Escherichia coli at 2.7-A resolution, which is to the authors' knowledge the first structure of an antibacterial peptide ABC transporter. Our functional and biochemical analyses demonstrate McjD-dependent immunity to MccJ25 through efflux of the peptide. McjD can directly bind MccJ25 and displays a basal ATPase activity that is stimulated by MccJ25 in both detergent solution and proteoliposomes. McjD adopts a new conformation, termed nucleotide-bound outward occluded. The new conformation defines a clear cavity; mutagenesis and ligand binding studies of the cavity have identified Phe86, Asn134, and Asn302 as important for recognition of MccJ25. Comparisons with the inward-open MsbA and outward-open Sav1866 structures show that McjD has structural similarities with both states without the intertwining of transmembrane (TM) helices. The occluded state is formed by rotation of TMs 1 and 2 toward the equivalent TMs of the opposite monomer, unlike Sav1866 where they intertwine with TMs 3-6 of the opposite monomer. Cysteine cross-linking studies on the McjD dimer in inside-out membrane vesicles of E. coli confirmed the presence of the occluded state. We therefore propose that the outward-occluded state represents a transition intermediate between the outward-open and inward-open conformation of ABC exporters.

Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state.,Choudhury HG, Tong Z, Mathavan I, Li Y, Iwata S, Zirah S, Rebuffat S, van Veen HW, Beis K Proc Natl Acad Sci U S A. 2014 Jun 11. pii: 201320506. PMID:24920594<ref>PMID:24920594</ref>

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ofr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
TOC
</StructureSection>
[[Category: Beis, K]]
[[Category: Bountra, K]]
[[Category: Abc transporter]]
[[Category: Adp-vo4]]
[[Category: Antibacterial peptide]]
[[Category: High energy outward occluded intermediate]]
[[Category: Membrane protein]]