title: Regulated oligomerisation and molecular interactions of the early gametocyte protein Pfg27 in Plasmodium falciparum sexual differentiation.
abstract: Gametocytes of the protozoan Plasmodium falciparum ensure malaria parasite transmission from humans to the insect vectors. In their development, they produce the abundant specific protein Pfg27, the function and in vivo molecular interactions of which are unknown. Here we reveal a previously unreported localisation of Pfg27 in the gametocyte nucleus by immunoelectron microscopy and studies with HaloTag and Green Fluorescent Protein fusions, and identify a network of interactions established by the protein during gametocyte development. We report the ability of endogenous Pfg27 to form oligomeric complexes that are affected by phosphorylation of the protein, possibly through the identified phosphorylation sites, Ser32 and Thr208. We show that Pfg27 binds RNA molecules through specific residues and that the protein interacts with parasite RNA-binding proteins such as EF1alpha and PfH45. We propose a structural model for Pfg27 oligomerisation, based on the sequence and structural conservation here recognised between Pfg27 and sterile alpha motif. This study provides a molecular basis for Pfg27 to establish an interaction network with RNA and RNA-binding proteins and to govern its dynamic oligomerisation in developing gametocytes.
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena n.299, 00161 Rome, Italy. grazia.camarda@iss.it
authors.forename: Grazia
authors.initials: G
authors.lastname: Camarda
authors.forename: Lucia
authors.initials: L
authors.lastname: Bertuccini
authors.forename: Saurabh Kumar
authors.initials: SK
authors.lastname: Singh
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Salzano
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lanfrancotti
authors.forename: Anna
authors.initials: A
authors.lastname: Olivieri
authors.forename: Andrea
authors.initials: A
authors.lastname: Scaloni
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
authors.forename: Pietro
authors.initials: P
authors.lastname: Alano
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000254:growth & development*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000378:metabolism*; D016053:RNA, Protozoan / Q000378:metabolism
chemical_list: D015800:Protozoan Proteins; D016053:RNA, Protozoan; C069962:Pfg25-27 protein, Plasmodium falciparum