6u23

From Proteopedia

(Difference between revisions)

Revision as of 01:05, 7 March 2020

EM structure of MPEG-1(w.t.) soluble pre-pore

6u23, resolution 3.49Å

Structural highlights

6u23 is a 16 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	MPEG1 (HUMAN)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MPEG1_HUMAN] Plays a key role in the innate immune response following bacterial infection by inserting into the bacterial surface to form pores (By similarity). 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 (By similarity). Shows antibacterial activity against a wide spectrum of Gram-positive, Gram-negative and acid-fast bacteria (PubMed:23753625, PubMed:26402460, PubMed:30609079). 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 (By similarity). Required for the antibacterial activity of reactive oxygen species and nitric oxide (By similarity).[UniProtKB:A1L314]^[1] ^[2] ^[3]

Publication Abstract from PubMed

Macrophage-expressed gene 1 (MPEG1/Perforin-2) is a perforin-like protein that functions within the phagolysosome to damage engulfed microbes. MPEG1 is thought to form pores in target membranes, however, its mode of action remains unknown. We use cryo-Electron Microscopy (cryo-EM) to determine the 2.4 A structure of a hexadecameric assembly of MPEG1 that displays the expected features of a soluble prepore complex. We further discover that MPEG1 prepore-like assemblies can be induced to perforate membranes through acidification, such as would occur within maturing phagolysosomes. We next solve the 3.6 A cryo-EM structure of MPEG1 in complex with liposomes. These data reveal that a multi-vesicular body of 12 kDa (MVB12)-associated beta-prism (MABP) domain binds membranes such that the pore-forming machinery of MPEG1 is oriented away from the bound membrane. This unexpected mechanism of membrane interaction suggests that MPEG1 remains bound to the phagolysosome membrane while simultaneously forming pores in engulfed bacterial targets.

The cryo-EM structure of the acid activatable pore-forming immune effector Macrophage-expressed gene 1.,Pang SS, Bayly-Jones C, Radjainia M, Spicer BA, Law RHP, Hodel AW, Parsons ES, Ekkel SM, Conroy PJ, Ramm G, Venugopal H, Bird PI, Hoogenboom BW, Voskoboinik I, Gambin Y, Sierecki E, Dunstone MA, Whisstock JC Nat Commun. 2019 Sep 19;10(1):4288. doi: 10.1038/s41467-019-12279-2. PMID:31537793^[4]

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

References

↑ 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
↑ Strbo N, Pastar I, Romero L, Chen V, Vujanac M, Sawaya AP, Jozic I, Ferreira ADF, Wong LL, Head C, Stojadinovic O, Garcia D, O'Neill K, Drakulich S, Taller S, Kirsner RS, Tomic-Canic M. Single cell analyses reveal specific distribution of anti-bacterial molecule Perforin-2 in human skin and its modulation by wounding and Staphylococcus aureus infection. Exp Dermatol. 2019 Mar;28(3):225-232. doi: 10.1111/exd.13870. Epub 2019 Feb 12. PMID:30609079 doi:http://dx.doi.org/10.1111/exd.13870
↑ Pang SS, Bayly-Jones C, Radjainia M, Spicer BA, Law RHP, Hodel AW, Parsons ES, Ekkel SM, Conroy PJ, Ramm G, Venugopal H, Bird PI, Hoogenboom BW, Voskoboinik I, Gambin Y, Sierecki E, Dunstone MA, Whisstock JC. The cryo-EM structure of the acid activatable pore-forming immune effector Macrophage-expressed gene 1. Nat Commun. 2019 Sep 19;10(1):4288. doi: 10.1038/s41467-019-12279-2. PMID:31537793 doi:http://dx.doi.org/10.1038/s41467-019-12279-2

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/6u23"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6u23 is ON HOLD
+==EM structure of MPEG-1(w.t.) soluble pre-pore==
+<SX load='6u23' size='340' side='right' viewer='molstar' caption='[[6u23]], [[Resolution|resolution]] 3.49&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6u23]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U23 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U23 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MPEG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6u23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u23 OCA], [http://pdbe.org/6u23 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u23 RCSB], [http://www.ebi.ac.uk/pdbsum/6u23 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u23 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/MPEG1_HUMAN MPEG1_HUMAN]] Plays a key role in the innate immune response following bacterial infection by inserting into the bacterial surface to form pores (By similarity). 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 (By similarity). Shows antibacterial activity against a wide spectrum of Gram-positive, Gram-negative and acid-fast bacteria (PubMed:23753625, PubMed:26402460, PubMed:30609079). 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 (By similarity). Required for the antibacterial activity of reactive oxygen species and nitric oxide (By similarity).[UniProtKB:A1L314]<ref>PMID:23753625</ref> <ref>PMID:26402460</ref> <ref>PMID:30609079</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Macrophage-expressed gene 1 (MPEG1/Perforin-2) is a perforin-like protein that functions within the phagolysosome to damage engulfed microbes. MPEG1 is thought to form pores in target membranes, however, its mode of action remains unknown. We use cryo-Electron Microscopy (cryo-EM) to determine the 2.4 A structure of a hexadecameric assembly of MPEG1 that displays the expected features of a soluble prepore complex. We further discover that MPEG1 prepore-like assemblies can be induced to perforate membranes through acidification, such as would occur within maturing phagolysosomes. We next solve the 3.6 A cryo-EM structure of MPEG1 in complex with liposomes. These data reveal that a multi-vesicular body of 12 kDa (MVB12)-associated beta-prism (MABP) domain binds membranes such that the pore-forming machinery of MPEG1 is oriented away from the bound membrane. This unexpected mechanism of membrane interaction suggests that MPEG1 remains bound to the phagolysosome membrane while simultaneously forming pores in engulfed bacterial targets.
-Authors:
+The cryo-EM structure of the acid activatable pore-forming immune effector Macrophage-expressed gene 1.,Pang SS, Bayly-Jones C, Radjainia M, Spicer BA, Law RHP, Hodel AW, Parsons ES, Ekkel SM, Conroy PJ, Ramm G, Venugopal H, Bird PI, Hoogenboom BW, Voskoboinik I, Gambin Y, Sierecki E, Dunstone MA, Whisstock JC Nat Commun. 2019 Sep 19;10(1):4288. doi: 10.1038/s41467-019-12279-2. PMID:31537793<ref>PMID:31537793</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 6u23" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</SX>
+[[Category: Human]]
+[[Category: Large Structures]]
+[[Category: Bayly-Jones, C]]
+[[Category: Pang, S S]]
+[[Category: Immune system]]
+[[Category: Immunity]]
+[[Category: Macpf]]
+[[Category: Macrophage]]
+[[Category: Mpeg-1/perforin-2]]
+[[Category: Pore forming protein]]

6u23

From Proteopedia

Revision as of 01:05, 7 March 2020

EM structure of MPEG-1(w.t.) soluble pre-pore

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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