Conformational co-dependence between Plasmodium berghei LCCL proteins promotes complex formation and stability
Year: 2012
Type: article
Abstract: This paper identifies conformational codependence between Plasmodium berghei LCCL proteins by crossing Pb LAP1-KO and Pb LAP3/GFP parasite lines. ► 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. 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 Pb LAP1 null mutant parasite with a parasite line expressing GFP-tagged Pb LAP3 that displays strong fluorescence in gametocytes. Selected and validated double mutants show normal synthesis and subcellular localization of Pb LAP3::GFP. However, GFP-based fluorescence is dramatically reduced without Pb LAP1 present, indicating that Pb LAP1 and Pb LAP3 interact. Moreover, absence of Pb LAP1 markedly reduces the half-life of Pb LAP3, 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.
Institution: London School of Hygiene & Tropical Medicine
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,460
OpenAlex ID: W2085960374