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| | ==SOLID-STATE NMR STRUCTURE OF PISCIDIN 1 IN ALIGNED 4:1 PHOSPHATIDYLCHOLINE/CHOLESTEROL LIPID BILAYERS== | | ==SOLID-STATE NMR STRUCTURE OF PISCIDIN 1 IN ALIGNED 4:1 PHOSPHATIDYLCHOLINE/CHOLESTEROL LIPID BILAYERS== |
| - | <StructureSection load='6pf0' size='340' side='right'caption='[[6pf0]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='6pf0' size='340' side='right'caption='[[6pf0]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6pf0]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PF0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PF0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6pf0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Morone_saxatilis Morone saxatilis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PF0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PF0 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=6pf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pf0 OCA], [http://pdbe.org/6pf0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pf0 RCSB], [http://www.ebi.ac.uk/pdbsum/6pf0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pf0 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=6pf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pf0 OCA], [https://pdbe.org/6pf0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pf0 RCSB], [https://www.ebi.ac.uk/pdbsum/6pf0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pf0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MORO_MORSA MORO_MORSA]] Exhibits broad spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria as well as against a variety of fungi. Has hemolytic activity. Seems to disrupt the membranes by adopting an alpha helical conformation and forming toroidal pores.<ref>PMID:11713517</ref> <ref>PMID:17253775</ref> | + | [https://www.uniprot.org/uniprot/MORO_MORSA MORO_MORSA] Exhibits broad spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria as well as against a variety of fungi. Has hemolytic activity. Seems to disrupt the membranes by adopting an alpha helical conformation and forming toroidal pores.<ref>PMID:11713517</ref> <ref>PMID:17253775</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cairns, L S]] | + | [[Category: Morone saxatilis]] |
| - | [[Category: Cotten, M L]] | + | [[Category: Cairns LS]] |
| - | [[Category: Fu, R]] | + | [[Category: Cotten ML]] |
| - | [[Category: Greenwood, A I]] | + | [[Category: Fu R]] |
| - | [[Category: Amphipathic]] | + | [[Category: Greenwood AI]] |
| - | [[Category: Anti hiv-1]]
| + | |
| - | [[Category: Anticancer peptide]]
| + | |
| - | [[Category: Antimicrobial peptide]]
| + | |
| - | [[Category: Antimicrobial protein]]
| + | |
| - | [[Category: Bacterial cell membrane mimic]]
| + | |
| - | [[Category: Cationic]]
| + | |
| - | [[Category: Helical]]
| + | |
| - | [[Category: Histidine rich]]
| + | |
| - | [[Category: Lipid bilayer]]
| + | |
| Structural highlights
Function
MORO_MORSA Exhibits broad spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria as well as against a variety of fungi. Has hemolytic activity. Seems to disrupt the membranes by adopting an alpha helical conformation and forming toroidal pores.[1] [2]
Publication Abstract from PubMed
The host-defense peptide (HDP) piscidin 1 (P1), isolated from the mast cells of striped bass, has potent activities against bacteria, viruses, fungi, and cancer cells and also can modulate the activity of membrane receptors. Given its broad pharmacological potential, here we used several approaches to better understand its interactions with multicomponent bilayers representing models of bacterial (phosphatidyl-ethanolamine/phosphatidylglycerol [PE/PG]) and mammalian (phosphatidyl-choline/cholesterol [PC/Chol]) membranes. Using solid-state NMR, we solved the structure of P1 bound to PC/Chol and compared it with that of P3, a less potent homolog. The comparison disclosed that although both peptides are interfacially bound and alpha-helical, they differ in bilayer orientations and depths of insertion, and these differences depended on bilayer composition. Although Chol is thought to make mammalian membranes less susceptible to HDP-mediated destabilization, we found that Chol does not affect the permeabilization effects of P1. X-ray diffraction experiments revealed that both piscidins produce a demixing effect in PC/Chol membranes by increasing the fraction of the Chol-depleted phase. Furthermore, P1 increased the temperature required for the lamellar-to-hexagonal phase transition in PE bilayers, suggesting that it imposes a positive membrane curvature. Patch-clamp measurements on the inner Escherichia coli membrane showed that P1 and P3 at concentrations sufficient for their antimicrobial activity substantially decrease the activating tension for bacterial mechanosensitive channels. This indicated that piscidins can cause lipid redistribution and restructuring in the microenvironment near proteins. We conclude that the mechanism of piscidin's antimicrobial activity extends beyond simple membrane destabilization, helping to rationalize its broader spectrum of pharmacological effects.
The host-defense peptide piscidin P1 reorganizes lipid domains in membranes and decreases activation energies in mechanosensitive ion channels.,Comert F, Greenwood A, Maramba J, Acevedo R, Lucas L, Kulasinghe T, Cairns LS, Wen Y, Fu R, Hammer J, Blazyk J, Sukharev S, Cotten ML, Mihailescu M J Biol Chem. 2019 Oct 16. pii: RA119.010232. doi: 10.1074/jbc.RA119.010232. PMID:31619519[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Silphaduang U, Noga EJ. Peptide antibiotics in mast cells of fish. Nature. 2001 Nov 15;414(6861):268-9. PMID:11713517 doi:http://dx.doi.org/10.1038/35104690
- ↑ Campagna S, Saint N, Molle G, Aumelas A. Structure and mechanism of action of the antimicrobial peptide piscidin. Biochemistry. 2007 Feb 20;46(7):1771-8. Epub 2007 Jan 25. PMID:17253775 doi:10.1021/bi0620297
- ↑ Comert F, Greenwood A, Maramba J, Acevedo R, Lucas L, Kulasinghe T, Cairns LS, Wen Y, Fu R, Hammer J, Blazyk J, Sukharev S, Cotten ML, Mihailescu M. The host-defense peptide piscidin P1 reorganizes lipid domains in membranes and decreases activation energies in mechanosensitive ion channels. J Biol Chem. 2019 Oct 16. pii: RA119.010232. doi: 10.1074/jbc.RA119.010232. PMID:31619519 doi:http://dx.doi.org/10.1074/jbc.RA119.010232
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