A multifunctional serine protease primes the malaria parasite for red blood cell invasion

• Konstantinos Koussis ^[1] ; Chrislaine Withers-Martinez ^[1] ; Sharon Yeoh ^[1] ; Matthew Child ^[1] ; Fiona Hackett ^[1] ; Ellen Knuepfer ^[1] ; Luiz Juliano ^[2] ; Ute Woehlbier ^[3] ; Hermann Bujard ^[3] ; Michael J Blackman ^[1]
  1. [1] National Institute for Medical Research

     National Institute for Medical Research

     Reino Unido

     
  2. [2] Universidade Federal de São Paulo

     Universidade Federal de São Paulo

     Brasil

     
  3. [3] Zentrum fuer Molekulare Biologie Heidelberg (ZMBH), Universitaet Heidelberg, Heidelberg, Germany

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 28, Nº. 6, 2009, págs. 725-735
• Idioma: inglés
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• Resumen

  • 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.