Structure and function of a unique pore-forming protein from a pathogenic Acanthamoeba

Michalek M1, Sönnichsen FD, Wechselberger R, Dingley AJ, Hung CW, Kopp A, Wienk H, Simanski M, Herbst R, Lorenzen I, Marciano-Cabral F, Gelhaus C, Gutsmann T, Tholey A, GrötzingerJ, Leippe M..

Nat Chem Biol. 2013 Jan; 9(1):37-42

Speaker: Kai-Fei Chang (張凱斐)                                        Time: 14:00~15:00, Apr. 9, 2014

Commentator: Dr. Shu-Ying Wang (王淑鶯 老師)             Place: Room 601

Abstract:

Acanthamoeba, a free-living amoeba, can cause amoebic keratitis and granulomatous amebic encephalitis. This kind of amoeba is isolated from water which is including natural and treated water in swimming pools and soil. Acanthamoeba keratitis patients who wear lenses while swimming or clean not enough their lenses increase infected risks. Granulomatous amebic encephalitis occurs in immunocompromised patients but the invasion pathways are still unclear¹. Pore-forming proteins are virulence factors and toxin in many pathogens producing such as bacteria and parasites. These proteins which make pores on cell membrane are characterized in Entamoeba histolytica and Naegleria fowleri for host tissue destruction^2,3. In this study, the authors discovered the structure and function of acanthaporin, a pore-form protein, which produces by Acanthamoeba. It makes neural cell damage by membrane-permeabilizing. The authors solved the structure ofacanthaporin by NMR spectroscopy, which the monomer is an active form. The mechanism of active form and inactive form switches which dependent on pH value. Monomer acanthaporinintegrates into cell membrane and makes membrane perforation. The pore formations lead to lyses target cell by braking membrane structure distribution. To summary, the author solvedacanthaporin structure and found evidences about the relationship between structure and function of acanthaporin. The pore-forming protein may play a pivotal role in Acanthamoeba invaded the human body.

References:

1.     Visvesvara GS. 2010. Amebic meningoencephalitides and keratitis: challenges in diagnosis and treatment. Curr Opin Infect Dis. Dec;23(6):590-4.

2.     Bruhn H. et al., 2003. Amoebapores and NK-lysin, members of a class of structurally distinct antimicrobial and cytolytic peptides from protozoa and mammals: a comparative functional analysis. Biochem J. 2003 Nov 1;375(Pt 3):737-44.

3.     Herbst R. et al., 2002. Pore-forming polypeptides of the pathogenic protozoon Naegleria fowleri. J Biol Chem. Jun 21;277(25):22353-60