Processing of metacaspase into a cytoplasmic catalytic domain mediating cell death in Leishmania major.

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Version: Final published version
Serval ID
serval:BIB_E32299FE64F3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Processing of metacaspase into a cytoplasmic catalytic domain mediating cell death in Leishmania major.
Journal
Molecular Microbiology
Author(s)
Zalila H., González I.J., El-Fadili A.K., Delgado M.B., Desponds C., Schaff C., Fasel N.
ISSN
1365-2958 (Electronic)
ISSN-L
0950-382X
Publication state
Published
Issued date
2011
Volume
79
Number
1
Pages
222-239
Language
english
Abstract
Metacaspases are cysteine peptidases that could play a role similar to caspases in the cell death programme of plants, fungi and protozoa. The human protozoan parasite Leishmania major expresses a single metacaspase (LmjMCA) harbouring a central domain with the catalytic dyad histidine and cysteine as found in caspases. In this study, we investigated the processing sites important for the maturation of LmjMCA catalytic domain, the cellular localization of LmjMCA polypeptides, and the functional role of the catalytic domain in the cell death pathway of Leishmania parasites. Although LmjMCA polypeptide precursor form harbours a functional mitochondrial localization signal (MLS), we determined that LmjMCA polypeptides are mainly localized in the cytoplasm. In stress conditions, LmjMCA precursor forms were extensively processed into soluble forms containing the catalytic domain. This domain was sufficient to enhance sensitivity of parasites to hydrogen peroxide by impairing the mitochondrion. These data provide experimental evidences of the importance of LmjMCA processing into an active catalytic domain and of its role in disrupting mitochondria, which could be relevant in the design of new drugs to fight leishmaniasis and likely other protozoan parasitic diseases.
Keywords
Amino Acid Sequence, Caspases/metabolism, Catalytic Domain, Cell Death, Cytoplasm/enzymology, Leishmania major/enzymology, Leishmania major/physiology, Mitochondria/enzymology, Molecular Sequence Data, Protein Processing, Post-Translational, Protein Transport, Sequence Alignment, Sequence Homology, Amino Acid
Pubmed
Web of science
Open Access
Yes
Create date
26/08/2011 8:25
Last modification date
20/08/2019 16:06
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