biostudies-literatureMartinez MAgence Nationale de la Recherchee0019824https://www.ebi.ac.uk/biostudies/studies/S-EPMC10936178biostudies-literatureUnknown15(3)Malaria symptoms are associated with the asexual multiplication of <i>Plasmodium falciparum</i> within human red blood cells (RBCs) and fever peaks coincide with the egress of daughter merozoites following the rupture of the parasitophorous vacuole (PV) and the RBC membranes. Over the last two decades, it has emerged that the release of competent merozoites is tightly regulated by a complex cascade of events, including the unusual multi-step activation mechanism of the pivotal subtilisin-like protease 1 (Sub1) that takes place in three different cellular compartments and remains poorly understood. Following an initial auto-maturation in the endoplasmic reticulum (ER) between its pro- and catalytic domains, the Sub1 prodomain (PD) undergoes further cleavages by the parasite aspartic proteasmBioProdomain-driven enzyme dimerization: a pH-dependent autoinhibition mechanism that controls <i>Plasmodium</i> Sub1 activity before merozoite egress.PMC10936178ANR-19-CE18-0010ANR-11-RPIB-002Alzari PMRaynal BMartinez MBouillon AHaouz ABrule SBarale J-CfalseProdomain-driven enzyme dimerization: a pH-dependent autoinhibition mechanism that controls <i>Plasmodium</i> Sub1 activity before merozoite egress.Malaria symptoms are associated with the asexual multiplication of <i>Plasmodium falciparum</i> within human red blood cells (RBCs) and fever peaks coincide with the egress of daughter merozoites following the rupture of the parasitophorous vacuole (PV) and the RBC membranes. Over the last two decades, it has emerged that the release of competent merozoites is tightly regulated by a complex cascade of events, including the unusual multi-step activation mechanism of the pivotal subtilisin-like protease 1 (Sub1) that takes place in three different cellular compartments and remains poorly understood. Following an initial auto-maturation in the endoplasmic reticulum (ER) between its pro- and catalytic domains, the Sub1 prodomain (PD) undergoes further cleavages by the parasite aspartic proteas2024-01-01T00:00:00Z2024 Mar2026-07-15T07:38:18.163Z2026-07-01T03:07:40.854ZS-EPMC109361783838659710.1128/mbio.00198-24