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< | ==Solution structure of the pore forming toxin of entamoeba histolytica (Amoebapore A)== | ||
<StructureSection load='1of9' size='340' side='right'caption='[[1of9]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1of9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Entamoeba_histolytica Entamoeba histolytica]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OF9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OF9 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=1of9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1of9 OCA], [https://pdbe.org/1of9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1of9 RCSB], [https://www.ebi.ac.uk/pdbsum/1of9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1of9 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PFPA_ENTH1 PFPA_ENTH1] Forms pores in the cell membrane of host cells (PubMed:14970207, PubMed:1881907, PubMed:7525351, PubMed:7715451, PubMed:8515772). Has antibacterial activity against M.luteus, no activity against E.coli (PubMed:7715451). Implicated in the cytolytic activity of the parasite (PubMed:7715451).<ref>PMID:14970207</ref> <ref>PMID:1881907</ref> <ref>PMID:7525351</ref> <ref>PMID:7715451</ref> <ref>PMID:8515772</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
== | Check<jmol> | ||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/of/1of9_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1of9 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Amoebapore A is a 77-residue protein from the protozoan parasite and human pathogen Entamoeba histolytica. Amoebapores lyse both bacteria and eukaryotic cells by pore formation and play a pivotal role in the destruction of host tissues during amoebiasis, one of the most life-threatening parasitic diseases. Amoebapore A belongs to the superfamily of saposin-like proteins that are characterized by a conserved disulfide bond pattern and a fold consisting of five helices. Membrane-permeabilizing effector molecules of mammalian lymphocytes such as porcine NK-lysin and the human granulysin share these structural attributes. Several mechanisms have been proposed to explain how saposin-like proteins form membrane pores. All mechanisms indicate that the surface charge distribution of these proteins is the basis of their membrane binding capacity and pore formation. Here, we have solved the structure of amoebapore A by NMR spectroscopy. We demonstrate that the specific activation step of amoebapore A depends on a pH-dependent dimerization event and is modulated by a surface-exposed histidine residue. Thus, histidine-mediated dimerization is the molecular switch for pore formation and reveals a novel activation mechanism of pore-forming toxins. | Amoebapore A is a 77-residue protein from the protozoan parasite and human pathogen Entamoeba histolytica. Amoebapores lyse both bacteria and eukaryotic cells by pore formation and play a pivotal role in the destruction of host tissues during amoebiasis, one of the most life-threatening parasitic diseases. Amoebapore A belongs to the superfamily of saposin-like proteins that are characterized by a conserved disulfide bond pattern and a fold consisting of five helices. Membrane-permeabilizing effector molecules of mammalian lymphocytes such as porcine NK-lysin and the human granulysin share these structural attributes. Several mechanisms have been proposed to explain how saposin-like proteins form membrane pores. All mechanisms indicate that the surface charge distribution of these proteins is the basis of their membrane binding capacity and pore formation. Here, we have solved the structure of amoebapore A by NMR spectroscopy. We demonstrate that the specific activation step of amoebapore A depends on a pH-dependent dimerization event and is modulated by a surface-exposed histidine residue. Thus, histidine-mediated dimerization is the molecular switch for pore formation and reveals a novel activation mechanism of pore-forming toxins. | ||
Solution structure of the pore-forming protein of Entamoeba histolytica.,Hecht O, Van Nuland NA, Schleinkofer K, Dingley AJ, Bruhn H, Leippe M, Grotzinger J J Biol Chem. 2004 Apr 23;279(17):17834-41. Epub 2004 Feb 17. PMID:14970207<ref>PMID:14970207</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1of9" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Entamoeba histolytica]] | [[Category: Entamoeba histolytica]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Bruhn | [[Category: Bruhn H]] | ||
[[Category: Dingley | [[Category: Dingley AJ]] | ||
[[Category: Grotzinger | [[Category: Grotzinger J]] | ||
[[Category: Hecht | [[Category: Hecht O]] | ||
[[Category: Leippe | [[Category: Leippe M]] | ||
[[Category: Schleinkofer K]] | |||
[[Category: Schleinkofer | [[Category: Van Nuland N]] | ||
[[Category: | |||
Latest revision as of 07:46, 17 October 2024
Solution structure of the pore forming toxin of entamoeba histolytica (Amoebapore A)Solution structure of the pore forming toxin of entamoeba histolytica (Amoebapore A)
Structural highlights
FunctionPFPA_ENTH1 Forms pores in the cell membrane of host cells (PubMed:14970207, PubMed:1881907, PubMed:7525351, PubMed:7715451, PubMed:8515772). Has antibacterial activity against M.luteus, no activity against E.coli (PubMed:7715451). Implicated in the cytolytic activity of the parasite (PubMed:7715451).[1] [2] [3] [4] [5] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAmoebapore A is a 77-residue protein from the protozoan parasite and human pathogen Entamoeba histolytica. Amoebapores lyse both bacteria and eukaryotic cells by pore formation and play a pivotal role in the destruction of host tissues during amoebiasis, one of the most life-threatening parasitic diseases. Amoebapore A belongs to the superfamily of saposin-like proteins that are characterized by a conserved disulfide bond pattern and a fold consisting of five helices. Membrane-permeabilizing effector molecules of mammalian lymphocytes such as porcine NK-lysin and the human granulysin share these structural attributes. Several mechanisms have been proposed to explain how saposin-like proteins form membrane pores. All mechanisms indicate that the surface charge distribution of these proteins is the basis of their membrane binding capacity and pore formation. Here, we have solved the structure of amoebapore A by NMR spectroscopy. We demonstrate that the specific activation step of amoebapore A depends on a pH-dependent dimerization event and is modulated by a surface-exposed histidine residue. Thus, histidine-mediated dimerization is the molecular switch for pore formation and reveals a novel activation mechanism of pore-forming toxins. Solution structure of the pore-forming protein of Entamoeba histolytica.,Hecht O, Van Nuland NA, Schleinkofer K, Dingley AJ, Bruhn H, Leippe M, Grotzinger J J Biol Chem. 2004 Apr 23;279(17):17834-41. Epub 2004 Feb 17. PMID:14970207[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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