Protease trafficking in two primitive eukaryotes is mediated by a prodomain protein motif

被引:76
作者
Huete-Pérez, JA
Engel, JC
Brinen, LS
Mottram, JC
McKerrow, JH
机构
[1] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94121 USA
[2] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94121 USA
[3] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94121 USA
[4] Univ Glasgow, Anderson Coll, Wellcome Unit Mol Parasitol, Glasgow G11 6NU, Lanark, Scotland
关键词
D O I
10.1074/jbc.274.23.16249
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Trypanosome protozoa, an early lineage of eukaryotic cells, have proteases homologous to mammalian lysosomal cathepsins, but the precursor proteins lack mannose 6-phosphate. Utilizing green fluorescent protein as a reporter, we demonstrate that the carbohydrate-free prodomain of a trypanosome cathepsin L is necessary and sufficient for directing green fluorescent protein to the lysosome/endosome compartment. A proper prodomain/catalytic domain processing site sequence is also required to free the mature protease for delivery to the lysosome/endosome compartment. A nine-amino acid prodomain loop motif, implicated in prodomain-receptor interactions in mammalian cells, is conserved in the protozoa, Site-directed mutagenesis now confirms the importance of this loop to protease trafficking and suggests that a protein motif targeting signal for lysosomal proteases arose early in eukaryotic cell evolution.
引用
收藏
页码:16249 / 16256
页数:8
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