Extensive proteolytic processing of the malaria parasite merozoite surface protein 7 during biosynthesis and parasite release from erythrocytes.
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.
Pachebat
Justin A
JA
Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London NW1 1AA, UK.
Kadekoppala
Madhusudan
M
Grainger
Munira
M
Dluzewski
Anton R
AR
Gunaratne
Ruwani S
RS
Scott-Finnigan
Terence J
TJ
Ogun
Solabomi A
SA
Ling
Irene T
IT
Bannister
Lawrence H
LH
Taylor
Helen M
HM
Mitchell
Graham H
GH
Holder
Anthony A
AA
D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron; D010447:Peptide Hydrolases / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000502:physiology* / Q000648:ultrastructure; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D052939:Schizonts / Q000378:metabolism; D013050:Spectrometry, Fluorescence
D008565:Membrane Proteins; D015800:Protozoan Proteins; C439571:merozoite surface protein 7, Plasmodium; D020126:Brefeldin A; D010447:Peptide Hydrolases