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

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• 作者：Sadia Saeed ; Annie Z. Tremp ; Johannes T. Dessens
• 关键词：Plasmodium berghei ; Crystalloid ; GFP ; Protein folding ; LCCL domain
• 刊名：Molecular and Biochemical Parasitology
• 出版年：2012
• 出版时间：October, 2012
• 年：2012
• 卷：185
• 期：2
• 页码：170-173
• 全文大小：433 K

文摘

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.