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Protein dolichylation in Plasmodium falciparum
Fabio Luiz D'Alexandri1, Emilia Akemi Kimura, Valnice Jesus Peres
1Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
FEBS Letters
|November 7, 2006
Summary
Plasmodium falciparum proteins contain dolichol, an 11-isoprene unit polyisoprenoid, attached post-translationally to cysteine residues. This discovery sheds light on parasite protein modification and potential drug targets.
Area of Science:
- Biochemistry
- Parasitology
- Molecular Biology
Background:
- Polyisoprenoids like dolichol are crucial for protein glycosylation in eukaryotes.
- Plasmodium falciparum, the parasite causing malaria, possesses unique biochemical pathways.
- Understanding protein modification in P. falciparum is key to identifying novel therapeutic targets.
Purpose of the Study:
- To identify and characterize polyisoprenoids attached to Plasmodium falciparum proteins.
- To elucidate the timing and mechanism of dolichol attachment to parasite proteins.
Main Methods:
- Reverse-phase thin-layer chromatography and high-performance liquid chromatography (RP-HPLC) for polyisoprenoid analysis.
- Sulfonium-salt cleavage with methyl iodide to release polyisoprenoids.
- Electrospray-ionization mass spectrometry for structural confirmation.
- Analysis of proteolytic digestion products and protein synthesis inhibitor treatments.
Main Results:
- Identified an 11-isoprene unit dolichol bound to 21-28-kDa protein clusters in P. falciparum trophozoite and schizont stages.
- Confirmed the dolichol structure using mass spectrometry.
- Demonstrated that dolichol attachment is a post-translational event, likely involving a covalent bond to cysteine residues.
Conclusions:
- Plasmodium falciparum utilizes dolichol, an 11-isoprene unit polyisoprenoid, for protein modification.
- Dolichol conjugation occurs post-translationally, suggesting a specific targeting mechanism to cysteine residues.
- This finding provides insights into P. falciparum's unique protein modification processes and potential vulnerabilities.
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