The malaria parasite egress protease SUB1 is a calcium-dependent redox switch subtilisin.


Withers-Martinez, C; Strath, M; Hackett, F; Haire, LF; Howell, SA; Walker, PA; Christodoulou, E; Evangelos, C; Dodson, GG; Blackman, MJ; (2014) The malaria parasite egress protease SUB1 is a calcium-dependent redox switch subtilisin. Nat Commun, 5. p. 3726. ISSN 2041-1723 DOI: https://doi.org/10.1038/ncomms4726

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Abstract

Malaria is caused by a protozoan parasite that replicates within an intraerythrocytic parasitophorous vacuole. Release (egress) of malaria merozoites from the host erythrocyte is a highly regulated and calcium-dependent event that is critical for disease progression. Minutes before egress, an essential parasite serine protease called SUB1 is discharged into the parasitophorous vacuole, where it proteolytically processes a subset of parasite proteins that play indispensable roles in egress and invasion. Here we report the first crystallographic structure of Plasmodium falciparum SUB1 at 2.25 Å, in complex with its cognate prodomain. The structure highlights the basis of the calcium dependence of SUB1, as well as its unusual requirement for interactions with substrate residues on both prime and non-prime sides of the scissile bond. Importantly, the structure also reveals the presence of a solvent-exposed redox-sensitive disulphide bridge, unique among the subtilisin family, that likely acts as a regulator of protease activity in the parasite.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 24785947
Web of Science ID: 337365300001
URI: http://researchonline.lshtm.ac.uk/id/eprint/1883887

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