8a1d

From Proteopedia

(Difference between revisions)

Current revision

Structure of murine perforin-2 (Mpeg1) pore in ring form

Structural highlights

8a1d is a 16 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MPEG1_MOUSE Plays a key role in the innate immune response following bacterial infection by polymerizing and inserting into the bacterial surface to form pores (PubMed:26402460). By breaching the surface of phagocytosed bacteria, allows antimicrobial effectors to enter the bacterial periplasmic space and degrade bacterial proteins such as superoxide dismutase sodC which contributes to bacterial virulence (PubMed:30249808). Shows antibacterial activity against a wide spectrum of Gram-positive, Gram-negative and acid-fast bacteria (PubMed:23257510, PubMed:23753625, PubMed:26402460). Reduces the viability of the intracytosolic pathogen L.monocytogenes by inhibiting acidification of the phagocytic vacuole of host cells which restricts bacterial translocation from the vacuole to the cytosol (PubMed:26831467). Required for the antibacterial activity of reactive oxygen species and nitric oxide (PubMed:26402460).^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Perforin-2 (PFN2, MPEG1) is a key pore-forming protein in mammalian innate immunity restricting intracellular bacteria proliferation. It forms a membrane-bound pre-pore complex that converts to a pore-forming structure upon acidification; but its mechanism of conformational transition has been debated. Here we used cryo-electron microscopy, tomography and subtomogram averaging to determine structures of PFN2 in pre-pore and pore conformations in isolation and bound to liposomes. In isolation and upon acidification, the pre-assembled complete pre-pore rings convert to pores in both flat ring and twisted conformations. On membranes, in situ assembled PFN2 pre-pores display various degrees of completeness; whereas PFN2 pores are mainly incomplete arc structures that follow the same subunit packing arrangements as found in isolation. Both assemblies on membranes use their P2 beta-hairpin for binding to the lipid membrane surface. Overall, these structural snapshots suggest a molecular mechanism for PFN2 pre-pore to pore transition on a targeted membrane, potentially using the twisted pore as an intermediate or alternative state to the flat conformation, with the capacity to cause bilayer distortion during membrane insertion.

Cryo-EM structures of perforin-2 in isolation and assembled on a membrane suggest a mechanism for pore formation.,Yu X, Ni T, Munson G, Zhang P, Gilbert RJC EMBO J. 2022 Dec 1;41(23):e111857. doi: 10.15252/embj.2022111857. Epub 2022 Oct , 17. PMID:36245269^[6]

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

References

↑ McCormack R, de Armas LR, Shiratsuchi M, Ramos JE, Podack ER. Inhibition of intracellular bacterial replication in fibroblasts is dependent on the perforin-like protein (perforin-2) encoded by macrophage-expressed gene 1. J Innate Immun. 2013;5(2):185-94. doi: 10.1159/000345249. Epub 2012 Dec 15. PMID:23257510 doi:http://dx.doi.org/10.1159/000345249
↑ Fields KA, McCormack R, de Armas LR, Podack ER. Perforin-2 restricts growth of Chlamydia trachomatis in macrophages. Infect Immun. 2013 Aug;81(8):3045-54. doi: 10.1128/IAI.00497-13. Epub 2013 Jun, 10. PMID:23753625 doi:http://dx.doi.org/10.1128/IAI.00497-13
↑ McCormack RM, de Armas LR, Shiratsuchi M, Fiorentino DG, Olsson ML, Lichtenheld MG, Morales A, Lyapichev K, Gonzalez LE, Strbo N, Sukumar N, Stojadinovic O, Plano GV, Munson GP, Tomic-Canic M, Kirsner RS, Russell DG, Podack ER. Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria. Elife. 2015 Sep 24;4. doi: 10.7554/eLife.06508. PMID:26402460 doi:http://dx.doi.org/10.7554/eLife.06508
↑ McCormack R, Bahnan W, Shrestha N, Boucher J, Barreto M, Barrera CM, Dauer EA, Freitag NE, Khan WN, Podack ER, Schesser K. Perforin-2 Protects Host Cells and Mice by Restricting the Vacuole to Cytosol Transitioning of a Bacterial Pathogen. Infect Immun. 2016 Mar 24;84(4):1083-1091. doi: 10.1128/IAI.01434-15. Print 2016 , Apr. PMID:26831467 doi:http://dx.doi.org/10.1128/IAI.01434-15
↑ Bai F, McCormack RM, Hower S, Plano GV, Lichtenheld MG, Munson GP. Perforin-2 Breaches the Envelope of Phagocytosed Bacteria Allowing Antimicrobial Effectors Access to Intracellular Targets. J Immunol. 2018 Nov 1;201(9):2710-2720. doi: 10.4049/jimmunol.1800365. Epub 2018 , Sep 24. PMID:30249808 doi:http://dx.doi.org/10.4049/jimmunol.1800365
↑ Yu X, Ni T, Munson G, Zhang P, Gilbert RJC. Cryo-EM structures of perforin-2 in isolation and assembled on a membrane suggest a mechanism for pore formation. EMBO J. 2022 Dec 1;41(23):e111857. PMID:36245269 doi:10.15252/embj.2022111857

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8a1d"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8a1d is ON HOLD
+==Structure of murine perforin-2 (Mpeg1) pore in ring form==
+<StructureSection load='8a1d' size='340' side='right'caption='[[8a1d]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8a1d]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A1D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A1D FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=8a1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a1d OCA], [https://pdbe.org/8a1d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a1d RCSB], [https://www.ebi.ac.uk/pdbsum/8a1d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a1d ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/MPEG1_MOUSE MPEG1_MOUSE] Plays a key role in the innate immune response following bacterial infection by polymerizing and inserting into the bacterial surface to form pores (PubMed:26402460). By breaching the surface of phagocytosed bacteria, allows antimicrobial effectors to enter the bacterial periplasmic space and degrade bacterial proteins such as superoxide dismutase sodC which contributes to bacterial virulence (PubMed:30249808). Shows antibacterial activity against a wide spectrum of Gram-positive, Gram-negative and acid-fast bacteria (PubMed:23257510, PubMed:23753625, PubMed:26402460). Reduces the viability of the intracytosolic pathogen L.monocytogenes by inhibiting acidification of the phagocytic vacuole of host cells which restricts bacterial translocation from the vacuole to the cytosol (PubMed:26831467). Required for the antibacterial activity of reactive oxygen species and nitric oxide (PubMed:26402460).<ref>PMID:23257510</ref> <ref>PMID:23753625</ref> <ref>PMID:26402460</ref> <ref>PMID:26831467</ref> <ref>PMID:30249808</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Perforin-2 (PFN2, MPEG1) is a key pore-forming protein in mammalian innate immunity restricting intracellular bacteria proliferation. It forms a membrane-bound pre-pore complex that converts to a pore-forming structure upon acidification; but its mechanism of conformational transition has been debated. Here we used cryo-electron microscopy, tomography and subtomogram averaging to determine structures of PFN2 in pre-pore and pore conformations in isolation and bound to liposomes. In isolation and upon acidification, the pre-assembled complete pre-pore rings convert to pores in both flat ring and twisted conformations. On membranes, in situ assembled PFN2 pre-pores display various degrees of completeness; whereas PFN2 pores are mainly incomplete arc structures that follow the same subunit packing arrangements as found in isolation. Both assemblies on membranes use their P2 beta-hairpin for binding to the lipid membrane surface. Overall, these structural snapshots suggest a molecular mechanism for PFN2 pre-pore to pore transition on a targeted membrane, potentially using the twisted pore as an intermediate or alternative state to the flat conformation, with the capacity to cause bilayer distortion during membrane insertion.
-Authors:
+Cryo-EM structures of perforin-2 in isolation and assembled on a membrane suggest a mechanism for pore formation.,Yu X, Ni T, Munson G, Zhang P, Gilbert RJC EMBO J. 2022 Dec 1;41(23):e111857. doi: 10.15252/embj.2022111857. Epub 2022 Oct , 17. PMID:36245269<ref>PMID:36245269</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8a1d" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Gilbert R]]
+[[Category: Ni T]]
+[[Category: Yu X]]
+[[Category: Zhang P]]

8a1d

From Proteopedia

Current revision

Structure of murine perforin-2 (Mpeg1) pore in ring form

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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