Article

Apicomplexan rhomboids have a potential role in microneme protein cleavage during host cell invasion.

Department of Biological Sciences, Imperial College London, Alexander Fleming Building, South Kensington Campus, London SW7 2AZ, UK.
International Journal for Parasitology (impact factor: 3.39). 07/2005; 35(7):747-56. DOI:10.1016/j.ijpara.2005.04.001
Source: PubMed

ABSTRACT Apicomplexan parasites secrete transmembrane (TM) adhesive proteins as part of the process leading to host cell attachment and invasion. These microneme proteins are cleaved in their TM domains by an unidentified protease termed microneme protein protease 1 (MPP1). The cleavage site sequence (IA downward arrowGG), mapped in the Toxoplasma gondii microneme proteins TgMIC2 and TgMIC6, is conserved in microneme proteins of other apicomplexans including Plasmodium species. We report here the characterisation of novel T. gondii proteins belonging to the rhomboid family of intramembrane-cleaving serine proteases. T. gondii possesses six genes encoding rhomboid-like proteins. Four are localised along the secretory pathway and therefore constitute possible candidates for MPP1 activity. Toxoplasma rhomboids TgROM1, TgROM2 and TgROM5 cleave the TM domain of Drosophila Spitz, an established substrate for rhomboids from several species, demonstrating that they are active proteases. In addition, TgROM2 cleaves chimeric proteins that contain the TM domains of TgMIC2 and TgMIC12.

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Keywords

cleavage site sequence
 
Drosophila Spitz
 
IA downward arrowGG
 
intramembrane-cleaving serine proteases
 
microneme protein protease 1
 
microneme proteins
 
MPP1
 
MPP1 activity
 
novel T. gondii proteins
 
Plasmodium species
 
TgMIC2
 
TgMIC6
 
TgROM2 cleaves chimeric proteins
 
TgROM5 cleave
 
TM
 
TM domain
 
TM domains
 
Toxoplasma gondii microneme proteins TgMIC2
 
Toxoplasma rhomboids TgROM1
 
unidentified protease
 

Timothy J Dowse