African trypanosomes have differentially expressed genes encoding homologues of the Leishmania GP63 surface protease.
The genomes of various Leishmania parasites contain tandemly arrayed genes encoding an abundant 63-kDa surface glycoprotein called GP63. Leishmania GP63s are metalloproteases that play an important role in the invasion and survival of the parasites within the macrophage, and their presence on the Leishmania surface has been correlated with resistance to complement-mediated lysis. Here we report the identification of GP63-like genes in African trypanosomes. The predicted trypanosome and Leishmania GP63s share a metalloprotease catalytic site motif of HEXXH as well as 19 cysteines and 10 prolines, implying a conservation of enzymatic activity and secondary/tertiary structure. The trypanosome GP63 genes are transcribed equally in procyclic and bloodstream trypanosomes, but their mRNAs accumulate to a 50-fold higher steady state level in bloodstream trypanosomes, where the ratio of mRNAs for GP63 and variant surface glycoprotein is about 1:150. Transcription of the GP63 genes is sensitive to alpha-amanitin, indicating that they are transcribed by a different polymerase than the variant surface glycoprotein genes. These results lead to a reconsideration of the potential functions of GP63, inasmuch as African trypanosomes are not known to interact with macrophages and do not have an intracellular stage during their life cycle.
El-Sayed
N M
NM
Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242, USA.
Donelson
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D003421:Crithidia / Q000235:genetics*; D018076:DNA, Complementary; D005786:Gene Expression Regulation; D017125:Genes, Protozoan; D008666:Metalloendopeptidases / Q000235:genetics*; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D016833:Trypanosoma brucei rhodesiense / Q000235:genetics*
D018076:DNA, Complementary; D015800:Protozoan Proteins; D008666:Metalloendopeptidases; C055146:glycoprotein gp63, Leishmania