1of9

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

1of9 is a 1 chain structure with sequence from Entamoeba histolytica. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 20 models
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).^[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 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.

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

↑ Hecht O, Van Nuland NA, Schleinkofer K, Dingley AJ, Bruhn H, Leippe M, Grotzinger J. Solution structure of the pore-forming protein of Entamoeba histolytica. J Biol Chem. 2004 Apr 23;279(17):17834-41. Epub 2004 Feb 17. PMID:14970207 doi:10.1074/jbc.M312978200
↑ Leippe M, Ebel S, Schoenberger OL, Horstmann RD, Müller-Eberhard HJ. Pore-forming peptide of pathogenic Entamoeba histolytica. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7659-63. PMID:1881907 doi:10.1073/pnas.88.17.7659
↑ Andrä J, Leippe M. Pore-forming peptide of Entamoeba histolytica. Significance of positively charged amino acid residues for its mode of action. FEBS Lett. 1994 Oct 31;354(1):97-102. PMID:7525351 doi:10.1016/0014-5793(94)01103-6
↑ Leippe M, Andrä J, Nickel R, Tannich E, Müller-Eberhard HJ. Amoebapores, a family of membranolytic peptides from cytoplasmic granules of Entamoeba histolytica: isolation, primary structure, and pore formation in bacterial cytoplasmic membranes. Mol Microbiol. 1994 Dec;14(5):895-904. PMID:7715451 doi:10.1111/j.1365-2958.1994.tb01325.x
↑ Leippe M, Bahr E, Tannich E, Horstmann RD. Comparison of pore-forming peptides from pathogenic and nonpathogenic Entamoeba histolytica. Mol Biochem Parasitol. 1993 May;59(1):101-9. PMID:8515772 doi:10.1016/0166-6851(93)90011-l
↑ Hecht O, Van Nuland NA, Schleinkofer K, Dingley AJ, Bruhn H, Leippe M, Grotzinger J. Solution structure of the pore-forming protein of Entamoeba histolytica. J Biol Chem. 2004 Apr 23;279(17):17834-41. Epub 2004 Feb 17. PMID:14970207 doi:10.1074/jbc.M312978200

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OCA

[1] Hecht O, Van Nuland NA, Schleinkofer K, Dingley AJ, Bruhn H, Leippe M, Grotzinger J. Solution structure of the pore-forming protein of Entamoeba histolytica. J Biol Chem. 2004 Apr 23;279(17):17834-41. Epub 2004 Feb 17. PMID:14970207 doi:10.1074/jbc.M312978200

[2] Leippe M, Ebel S, Schoenberger OL, Horstmann RD, Müller-Eberhard HJ. Pore-forming peptide of pathogenic Entamoeba histolytica. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7659-63. PMID:1881907 doi:10.1073/pnas.88.17.7659

[3] Andrä J, Leippe M. Pore-forming peptide of Entamoeba histolytica. Significance of positively charged amino acid residues for its mode of action. FEBS Lett. 1994 Oct 31;354(1):97-102. PMID:7525351 doi:10.1016/0014-5793(94)01103-6

[4] Leippe M, Andrä J, Nickel R, Tannich E, Müller-Eberhard HJ. Amoebapores, a family of membranolytic peptides from cytoplasmic granules of Entamoeba histolytica: isolation, primary structure, and pore formation in bacterial cytoplasmic membranes. Mol Microbiol. 1994 Dec;14(5):895-904. PMID:7715451 doi:10.1111/j.1365-2958.1994.tb01325.x

[5] Leippe M, Bahr E, Tannich E, Horstmann RD. Comparison of pore-forming peptides from pathogenic and nonpathogenic Entamoeba histolytica. Mol Biochem Parasitol. 1993 May;59(1):101-9. PMID:8515772 doi:10.1016/0166-6851(93)90011-l

[6] Hecht O, Van Nuland NA, Schleinkofer K, Dingley AJ, Bruhn H, Leippe M, Grotzinger J. Solution structure of the pore-forming protein of Entamoeba histolytica. J Biol Chem. 2004 Apr 23;279(17):17834-41. Epub 2004 Feb 17. PMID:14970207 doi:10.1074/jbc.M312978200

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