Molecular dissection of novel trafficking and processing of the Toxoplasma gondii rhoptry metalloprotease toxolysin-1.
Traffic
; 13(2): 292-304, 2012 Feb.
Article
in En
| MEDLINE
| ID: mdl-22035499
ABSTRACT
Toxoplasma gondii utilizes specialized secretory organelles called rhoptries to invade and hijack its host cell. Many rhoptry proteins are proteolytically processed at a highly conserved SΦXE site to remove organellar targeting sequences that may also affect protein activity. We have studied the trafficking and biogenesis of a secreted rhoptry metalloprotease with homology to insulysin that we named toxolysin-1 (TLN1). Through genetic ablation and molecular dissection of TLN1, we have identified the smallest rhoptry targeting domain yet reported and expanded the consensus sequence of the rhoptry pro-domain cleavage site. In addition to removal of its pro-domain, TLN1 undergoes a C-terminal cleavage event that occurs at a processing site not previously seen in Toxoplasma rhoptry proteins. While pro-domain cleavage occurs in the nascent rhoptries, processing of the C-terminal region precedes commitment to rhoptry targeting, suggesting that it is mediated by a different maturase, and we have identified residues critical for proteolysis. We have additionally shown that both pieces of TLN1 associate in a detergent-resistant complex, formation of which is necessary for trafficking of the C-terminal portion to the rhoptries. Together, these studies reveal novel processing and trafficking events that are present in the protein constituents of this unusual secretory organelle.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Toxoplasma
/
Metalloendopeptidases
/
Protozoan Proteins
/
Protein Processing, Post-Translational
/
Protein Transport
Language:
En
Journal:
Traffic
Journal subject:
FISIOLOGIA
Year:
2012
Document type:
Article
Affiliation country:
United States