Short communicationConformational co-dependence between Plasmodium berghei LCCL proteins promotes complex formation and stability

Malaria parasites express a conserved family of LCCL-lectin adhesive-like domain proteins (LAPs) that have essential functions in sporozoite transmission. In Plasmodium falciparum all six family members are expressed in gametocytes and form a multi-protein complex. Intriguingly, knockout of P. falciparum LCCL proteins adversely affects expression of other family members at protein, but not at mRNA level, a phenomenon termed co-dependent expression. Here, we investigate this in Plasmodium berghei by crossing a PbLAP1 null mutant parasite with a parasite line expressing GFP-tagged PbLAP3 that displays strong fluorescence in gametocytes. Selected and validated double mutants show normal synthesis and subcellular localization of PbLAP3::GFP. However, GFP-based fluorescence is dramatically reduced without PbLAP1 present, indicating that PbLAP1 and PbLAP3 interact. Moreover, absence of PbLAP1 markedly reduces the half-life of PbLAP3, consistent with a scenario of misfolding. These findings unveil a potential mechanism of conformational interdependence that facilitates assembly and stability of the functional LCCL protein complex.

Graphical abstractThis paper identifies conformational codependence between Plasmodium berghei LCCL proteins by crossing PbLAP1-KO and PbLAP3/GFP parasite lines.Download high-res image (160KB)Download full-size imageHighlight► Co-dependent expression of LCCL proteins appears absent in Plasmodium berghei. ► However, P. berghei LCCL proteins are conformationally co-dependent. ► This mechanism promotes LCCL protein complex formation and stability. ► Conformational co-dependence could be the mechanism behind co-dependent expression.