Hemoglobin-degrading plasmepsin II is active as a monomer.
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 PM II monomer surface, which would be buried in a PM II dimer, is shown to be essential for the hemoglobin degradation capability of PM II.
Liu
Jun
J
Departments of Molecular Microbiology and Medicine, Washington University School of Medicine, Howard Hughes Medical Institute, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Istvan
Eva S
ES
Goldberg
Daniel E
DE
D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001483:Base Sequence; D020059:Cathepsin E / Q000378:metabolism; D002850:Chromatography, Gel; D017931:DNA Primers; D006454:Hemoglobins / Q000378:metabolism*; D008958:Models, Molecular; D016296:Mutagenesis; D015800:Protozoan Proteins
D017931:DNA Primers; D006454:Hemoglobins; D015800:Protozoan Proteins; D016282:Aspartic Acid Endopeptidases; D020059:Cathepsin E; C100637:plasmepsin II