SERA6 and its partner MSA180 form transient multimolecular aggregates during egress. Representative IFA images demonstrating the dynamic changes in localisation of SERA6-mTAP during egress (reproducible in 4 independent experiments). SERA6-mTAP:loxP schizonts were sampled at the indicated times following removal of C2-arrest, fixed and co-stained with DAPI (blue), anti-HA (red) and anti-ankyrin (green; ankyrin is a major component of the RBC cytoskeleton). Scale bar, 5 mm. Within 5 min of C2 removal, the HA signal altered dramatically to appear as distinct, punctate foci, indicating coalescence of the SERA6 into multiple intracellular condensates or aggregates (A), B Z-stack series of a representative schizont demonstrating that SERA6 aggregates observed during egress are distributed throughout the schizont. SERA6-mTAP:loxP schizonts sampled 5 min following removal of C2-arrest were fixed and co-stained with anti-HA (red) and anti-ankyrin (green), then imaged on an Olympus FLUOVIEW FV3000. Scale bar, 5 mm, This confirmed that the foci were distributed throughout the schizont volume, although a few were co-localized with ankyrin, indicating association with the RBC cytoskeleton (B).

Tan MSY, Koussis K, Withers-Martinez C, Howell SA, Thomas JA, Hackett F, Knuepfer E, Shen M, Hall MD, Snijders AP, Blackman MJ. Autocatalytic activation of a malarial egress protease is druggable and requires a protein cofactor. EMBO J. 2021 1:e107226.