Extensive proteolytic processing of the malaria parasite merozoite surface protein 7 during biosynthesis and parasite release from erythrocytes

Justin A Pachebat, Madhusudan Kadekoppala, Munira Grainger, Anton R Dluzewski, Ruwani S Gunaratne, Terence J Scott-Finnigan, Solabomi A Ogun, Irene T Ling, Lawrence H. Bannister, Helen M Taylor, Graham H Mitchell, Anthony A Holder

Research output: Contribution to journalArticlepeer-review

44 Citations (SciVal)

Abstract

In Plasmodium falciparum, merozoite surface protein 7 (MSP7) was originally identified as a 22kDa protein on the merozoite surface and associated with the MSP1 complex shed during erythrocyte invasion. MSP7 is synthesised in schizonts as a 351-amino acid precursor that undergoes proteolytic processing. During biosynthesis the MSP1 and MSP7 precursors form a complex that is targeted to the surface of developing merozoites. In the sequential proteolytic processing of MSP7, N- and C-terminal 20 and 33kDa products of primary processing, MSP7(20) and MSP7(33) are formed and MSP7(33) remains bound to full length MSP1. Later in the mature schizont, MSP7(20) disappears from the merozoite surface and on merozoite release MSP7(33) undergoes a secondary cleavage yielding the 22kDa MSP7(22) associated with MSP1. In free merozoites, both MSP7(22) and a further cleaved product, MSP7(19) present only in some parasite lines, were detected; these two derivatives are shed as part of the protein complex with MSP1 fragments during erythrocyte invasion. Primary processing of MSP7 is brefeldin A-sensitive while secondary processing is resistant to both calcium chelators and serine protease inhibitors. Primary processing of MSP7 occurs prior to that of MSP1 in a post-Golgi compartment, whereas the secondary cleavage occurs on the surface of the developing merozoite, possibly at the time of MSP1 primary processing and well before the secondary processing of MSP1.

Original languageEnglish
Pages (from-to)59-69
Number of pages11
JournalMolecular and Biochemical Parasitology
Volume151
Issue number1
Early online date02 Nov 2006
DOIs
Publication statusPublished - Jan 2007

Keywords

  • Animals
  • Brefeldin A
  • Erythrocytes
  • Membrane Proteins
  • Microscopy, Electron, Transmission
  • Microscopy, Immunoelectron
  • Peptide Hydrolases
  • Plasmodium falciparum
  • Protein Binding
  • Protein Biosynthesis
  • Protein Processing, Post-Translational
  • Protozoan Proteins
  • Schizonts
  • Spectrometry, Fluorescence

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