A multifunctional serine protease primes the malaria parasite for red blood cell invasion.
The malaria parasite Plasmodium falciparum replicates within an intraerythrocytic parasitophorous vacuole (PV). Rupture of the host cell allows release (egress) of daughter merozoites, which invade fresh erythrocytes. We previously showed that a subtilisin-like protease called PfSUB1 regulates egress by being discharged into the PV in the final stages of merozoite development to proteolytically modify the SERA family of papain-like proteins. Here, we report that PfSUB1 has a further role in 'priming' the merozoite prior to invasion. The major protein complex on the merozoite surface comprises three proteins called merozoite surface protein 1 (MSP1), MSP6 and MSP7. We show that just before egress, all undergo proteolytic maturation by PfSUB1. Inhibition of PfSUB1 activity results in the accumulation of unprocessed MSPs on the merozoite surface, and erythrocyte invasion is significantly reduced. We propose that PfSUB1 is a multifunctional processing protease with an essential role in both egress of the malaria merozoite and remodelling of its surface in preparation for erythrocyte invasion.
Koussis
Konstantinos
K
Division of Parasitology, National Institute for Medical Research, London, UK.
Withers-Martinez
Chrislaine
C
Yeoh
Sharon
S
Child
Matthew
M
Hackett
Fiona
F
Knuepfer
Ellen
E
Juliano
Luiz
L
Woehlbier
Ute
U
Bujard
Hermann
H
Blackman
Michael J
MJ
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D016384:Consensus Sequence; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology*; D006801:Humans; D016778:Malaria, Falciparum / Q000201:enzymology* / Q000469:parasitology*; D052940:Merozoites / Q000201:enzymology; D008969:Molecular Sequence Data; D010271:Parasites / Q000187:drug effects / Q000201:enzymology*; D010455:Peptides / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013379:Substrate Specificity / Q000187:drug effects; D013381:Subtilisins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
D010455:Peptides; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D013381:Subtilisins; C403176:subtilisin-like protease 1, Plasmodium falciparum