• 1 Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, DE, Malaysia
  • 2 Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, Guelph, ON N1G 2W1, Canada
  • 3 Department of Food Science & Technology, College of Agricultural and Environmental Sciences, University of Georgia, 100 Cedar Street, Athens, GA 30602, United States
  • 4 Department of Food Science, Ontario Agricultural College, University of Guelph, Guelph, ON N1G 2W1, Canada
  • 5 Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India
  • 6 Faculty of Land and Food Systems, University of British Columbia, MacMillan Building, 2357 Main Mall, Vancouver, BC V6T 1Z4, Canada. Electronic address:
Biochim. Biophys. Acta, 2016 10;1864(10):1356-62.
PMID: 27378574 DOI: 10.1016/j.bbapap.2016.06.019


Plasmepsin II is a malarial pepsin-like aspartic protease produced as a zymogen containing an N-terminal prosegment domain that is removed during activation. Despite structural similarities between active plasmepsin II and pepsin, their prosegments adopt different conformations in the respective zymogens. In contrast to pepsinogen, the proplasmepsin II prosegment is 80 residues longer, contains a transmembrane region and is non-essential for recombinant expression in an active form, thus calling into question the prosegment's precise function. The present study examines the role of the prosegment in the folding mechanism of plasmepsin II. Both a shorter (residues 77-124) and a longer (residues 65-124) prosegment catalyze plasmepsin II folding at rates more than four orders of magnitude faster compared to folding without prosegment. Native plasmepsin II is kinetically trapped and requires the prosegment both to catalyze folding and to shift the folding equilibrium towards the native conformation. Thus, despite low sequence identity and distinct zymogen conformations, the folding landscapes of plasmepsin II and pepsin, both with and without prosegment, are qualitatively identical. These results imply a conserved and unusual feature of the pepsin-like protease topology that necessitates prosegment-assisted folding.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.