Interaction of Leishmania PTS2 receptor peroxin 7 with the glycosomal protein import machinery

Leishmania proteins containing a peroxisomal targeting signal sequence 2 (PTS2) are selectively trafficked to the glycosome by associating with the peroxin 7 receptor protein (PEX7). The L. major PEX7 (LmPEX7) encodes a ∼41 kDa protein that exhibits limited sequence identity with PEX7 homologues from other eukaryotic organisms. Functional characterization of recombinant and native LmPEX7 revealed that this receptor bound the PTS2 protein fructose-1,6-bisphosphate aldolase. Moreover, LmPEX7 also formed a tight association with the Leishmania PEX5, the cytosolic PTS1 receptor, and PEX14, a glycosomal peripheral membrane protein required for protein import into the glycosome. Mapping studies revealed that the Leishmania PEX7 binds to a domain on LdPEX5 encompassing residues 111–148 and to a site on LdPEX14 spanning residues 120–148. Finally, subcellular localization studies revealed that Leishmania PEX7 has a dual distribution within the cytosolic compartment and glycosomal lumen.