Hemoglobin-degrading plasmepsin II is active as a monomer

Abstract

A family of aspartic proteases called plasmepsins is important for hemoglobin degradation in intraerythrocytic Plasmodium parasites. Plasmepsin II (PM II) is the best studied member of this family. PM II and its close orthologs and paralogs form homodimers with extensive interfaces in all known crystal structures. This raised the question whether the homodimer is the functional subunit of plasmepsins in solution. We have used gel filtration chromatography, site-directed mutagenesis, and analytical ultracentrifugation to study the oligomeric status of PM II in solution. Our results reveal that PM II exists mainly as a monomer in solution and that the monomer is fully functional for catalysis. A hydrophobic loop at the PMII monomer surface, which would be buried in a PMII dimer, is shown to be essential for the hemoglobin degradation capability of PM II. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.