Trypanosoma brucei Metacaspase 4 Is a Pseudopeptidase and a Virulence Factor*

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Trypanosoma brucei Metacaspase 4 Is a Pseudopeptidase and a Virulence Factor*

Metacaspases are caspase family cysteine peptidases found in plants, fungi, and protozoa but not mammals. Trypanosoma brucei is unusual in having five metacaspases (MCA1-MCA5), of which MCA1 and MCA4 have active site substitutions, making them possible non-enzymatic homologues. Here we demonstrate that recombinant MCA4 lacks detectable peptidase activity despite maintaining a functional peptida...

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Crystal structure of a Trypanosoma brucei metacaspase.

Metacaspases are distantly related caspase-family cysteine peptidases implicated in programmed cell death in plants and lower eukaryotes. They differ significantly from caspases because they are calcium-activated, arginine-specific peptidases that do not require processing or dimerization for activity. To elucidate the basis of these differences and to determine the impact they might have on th...

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Substrate specificity and the effect of calcium on Trypanosoma brucei metacaspase 2.

Metacaspases are cysteine peptidases found only in yeast, plants and lower eukaryotes, including the protozoa. To investigate the extended substrate specificity and effects of Ca(2+) on the activation of these enzymes, detailed kinetic, biochemical and structural analyses were carried out on metacaspase 2 from Trypanosoma brucei (TbMCA2). These results reveal that TbMCA2 has an unambiguous pref...

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Extracellular Vesicles from Trypanosoma brucei Mediate Virulence Factor Transfer and Cause Host Anemia

Intercellular communication between parasites and with host cells provides mechanisms for parasite development, immune evasion, and disease pathology. Bloodstream African trypanosomes produce membranous nanotubes that originate from the flagellar membrane and disassociate into free extracellular vesicles (EVs). Trypanosome EVs contain several flagellar proteins that contribute to virulence, and...

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Trypanosoma brucei brucei

Protein synthesis in Trypanosoma brucei brucei was rapidly inhibited during polyamine depletion by DL-adifluoromethylornithine (DFMO) in vitro and in vivo. [3H]Leucine incorporation was depressed 30-40 % by 24 h and 80-90 % by 48 h of DFMO treatment. Concomitantly there was an apparent decrease in the synthesis of the variant-specific glycoprotein (VSG) in DFMO-treated trypanosomes, as measured...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 2011

ISSN: 0021-9258

DOI: 10.1074/jbc.m111.292334