期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 284, 期 39, 页码 26839-26850出版社
ELSEVIER
DOI: 10.1074/jbc.M109.003780
关键词
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资金
- National Institutes of Health [RR020843, GM64655, AI067921, AI063263]
- Stanley Medical Research Institute [04R-796]
- Department of Energy, Office of Biological and Environmental Research
- National Institutes of Health, National Center for Research Resources, Biomedical Technology Program
- NIGMS
The protozoan parasite Toxoplasma gondii relies on posttranslational modification, including proteolysis, of proteins required for recognition and invasion of host cells. We have characterized the T. gondii cysteine protease cathepsin L (TgCPL), one of five cathepsins found in the T. gondii genome. We show that TgCPL is the primary target of the compound morpholinurea-leucyl-homophenyl-vinyl sulfone phenyl (LHVS), which was previously shown to inhibit parasite invasion by blocking the release of invasion proteins from microneme secretory organelles. As shown by fluorescently labeled LHVS and TgCPL-specific antibodies, TgCPL is associated with a discrete vesicular structure in the apical region of extracellular parasites but is found in multiple puncta throughout the cytoplasm of intracellular replicating parasites. LHVS fails to label cells lacking TgCPL due to targeted disruption of the TgCPL gene in two different parasite strains. We present a structural model for the inhibition of TgCPL by LHVS based on a 2.0 angstrom resolution crystal structure of TgCPL in complex with its propeptide. We discuss possible roles for TgCPL as a protease involved in the degradation or limited proteolysis of parasite proteins involved in invasion.
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