5odw: Difference between revisions
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==Structure of the FpvAI-pyocin S2 complex== | |||
<StructureSection load='5odw' size='340' side='right' caption='[[5odw]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5odw]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ODW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ODW FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5odw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5odw OCA], [http://pdbe.org/5odw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5odw RCSB], [http://www.ebi.ac.uk/pdbsum/5odw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5odw ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/FPVA_PSEAE FPVA_PSEAE]] Receptor for the siderophore ferripyoverdine. [[http://www.uniprot.org/uniprot/PYS2_PSEAE PYS2_PSEAE]] Causes breakdown of chromosomal DNA as well as complete inhibition of lipid synthesis in sensitive cells. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Unlike their descendants, mitochondria and plastids, bacteria do not have dedicated protein import systems. However, paradoxically, import of protein bacteriocins, the mechanisms of which are poorly understood, underpins competition among pathogenic and commensal bacteria alike. Here, using X-ray crystallography, isothermal titration calorimetry, confocal fluorescence microscopy, and in vivo photoactivatable cross-linking of stalled translocation intermediates, we demonstrate how the iron transporter FpvAI in the opportunistic pathogen Pseudomonas aeruginosa is hijacked to translocate the bacteriocin pyocin S2 (pyoS2) across the outer membrane (OM). FpvAI is a TonB-dependent transporter (TBDT) that actively imports the small siderophore ferripyoverdine (Fe-Pvd) by coupling to the proton motive force (PMF) via the inner membrane (IM) protein TonB1. The crystal structure of the N-terminal domain of pyoS2 (pyoS2NTD) bound to FpvAI (Kd = 240 pM) reveals that the pyocin mimics Fe-Pvd, inducing the same conformational changes in the receptor. Mimicry leads to fluorescently labeled pyoS2NTD being imported into FpvAI-expressing P. aeruginosa cells by a process analogous to that used by bona fide TBDT ligands. PyoS2NTD induces unfolding by TonB1 of a force-labile portion of the plug domain that normally occludes the central channel of FpvAI. The pyocin is then dragged through this narrow channel following delivery of its own TonB1-binding epitope to the periplasm. Hence, energized nutrient transporters in bacteria also serve as rudimentary protein import systems, which, in the case of FpvAI, results in a protein antibiotic 60-fold bigger than the transporter's natural substrate being translocated across the OM. | |||
Exploitation of an iron transporter for bacterial protein antibiotic import.,White P, Joshi A, Rassam P, Housden NG, Kaminska R, Goult JD, Redfield C, McCaughey LC, Walker D, Mohammed S, Kleanthous C Proc Natl Acad Sci U S A. 2017 Oct 25. pii: 201713741. doi:, 10.1073/pnas.1713741114. PMID:29078392<ref>PMID:29078392</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5odw" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Joshi, A]] | |||
[[Category: Kleanthous, C]] | |||
[[Category: White, P]] | |||
[[Category: Antimicrobial protein]] | |||
[[Category: Membrane protein complex]] | |||
[[Category: Protein transport]] | |||
Revision as of 10:34, 8 November 2017
Structure of the FpvAI-pyocin S2 complexStructure of the FpvAI-pyocin S2 complex
Structural highlights
Function[FPVA_PSEAE] Receptor for the siderophore ferripyoverdine. [PYS2_PSEAE] Causes breakdown of chromosomal DNA as well as complete inhibition of lipid synthesis in sensitive cells. Publication Abstract from PubMedUnlike their descendants, mitochondria and plastids, bacteria do not have dedicated protein import systems. However, paradoxically, import of protein bacteriocins, the mechanisms of which are poorly understood, underpins competition among pathogenic and commensal bacteria alike. Here, using X-ray crystallography, isothermal titration calorimetry, confocal fluorescence microscopy, and in vivo photoactivatable cross-linking of stalled translocation intermediates, we demonstrate how the iron transporter FpvAI in the opportunistic pathogen Pseudomonas aeruginosa is hijacked to translocate the bacteriocin pyocin S2 (pyoS2) across the outer membrane (OM). FpvAI is a TonB-dependent transporter (TBDT) that actively imports the small siderophore ferripyoverdine (Fe-Pvd) by coupling to the proton motive force (PMF) via the inner membrane (IM) protein TonB1. The crystal structure of the N-terminal domain of pyoS2 (pyoS2NTD) bound to FpvAI (Kd = 240 pM) reveals that the pyocin mimics Fe-Pvd, inducing the same conformational changes in the receptor. Mimicry leads to fluorescently labeled pyoS2NTD being imported into FpvAI-expressing P. aeruginosa cells by a process analogous to that used by bona fide TBDT ligands. PyoS2NTD induces unfolding by TonB1 of a force-labile portion of the plug domain that normally occludes the central channel of FpvAI. The pyocin is then dragged through this narrow channel following delivery of its own TonB1-binding epitope to the periplasm. Hence, energized nutrient transporters in bacteria also serve as rudimentary protein import systems, which, in the case of FpvAI, results in a protein antibiotic 60-fold bigger than the transporter's natural substrate being translocated across the OM. Exploitation of an iron transporter for bacterial protein antibiotic import.,White P, Joshi A, Rassam P, Housden NG, Kaminska R, Goult JD, Redfield C, McCaughey LC, Walker D, Mohammed S, Kleanthous C Proc Natl Acad Sci U S A. 2017 Oct 25. pii: 201713741. doi:, 10.1073/pnas.1713741114. PMID:29078392[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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