title: Conformational co-dependence between Plasmodium berghei LCCL proteins promotes complex formation and stability.
abstract: 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.
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Sadia
authors.initials: S
authors.lastname: Saeed
authors.forename: Annie Z
authors.initials: AZ
authors.lastname: Tremp
authors.forename: Johannes T
authors.initials: JT
authors.lastname: Dessens
mesh_terms: D000818:Animals; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D037102:Lectins / Q000737:chemistry / Q000235:genetics; D009154:Mutation; D010962:Plasmodium berghei / Q000737:chemistry / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D034101:Sporozoites / Q000378:metabolism
chemical_list: D037102:Lectins; D015800:Protozoan Proteins; D049452:Green Fluorescent Proteins