title: Structural and functional dissection of Toxoplasma gondii armadillo repeats only protein.
abstract: Rhoptries are club-shaped, regulated secretory organelles that cluster at the apical pole of apicomplexan parasites. Their discharge is essential for invasion and the establishment of an intracellular lifestyle. Little is known about rhoptry biogenesis and recycling during parasite division. In Toxoplasma gondii, positioning of rhoptries involves the armadillo repeats only protein (ARO) and myosin F (MyoF). Here, we show that two ARO partners, ARO-interacting protein (AIP) and adenylate cyclase β (ACβ) localize to a rhoptry subcompartment. In absence of AIP, ACβ disappears from the rhoptries. By assessing the contribution of each ARO armadillo (ARM) repeat, we provide evidence that ARO is multifunctional, participating not only in positioning but also in clustering of rhoptries. Structural analyses show that ARO resembles the myosin-binding domain of the Caenorhabditis elegans myosin chaperone UNC-45. A conserved patch of aromatic and acidic residues denotes the putative MyoF-binding site, and the overall arrangement of the ARM repeats explains the dramatic consequences of deleting each of them. Finally, Plasmodium falciparum ARO functionally complements ARO depletion and interacts with the same partners, highlighting the conservation of rhoptry biogenesis in Apicomplexa.
authors.affiliation: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 Rue Michel-Servet, CH-1211, Geneva 4, Switzerland.
authors.forename: Christina
authors.initials: C
authors.lastname: Mueller
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5400, Oulu 90014, Finland Helmholtz Centre for Infection Research, Notkestrasse 85, Hamburg 22607, Germany German Electron Synchrotron (DESY), Notkestrasse 85, Hamburg 22607, Germany.
authors.forename: Atta
authors.initials: A
authors.lastname: Samoo
authors.affiliation: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 Rue Michel-Servet, CH-1211, Geneva 4, Switzerland.
authors.forename: Pierre-Mehdi
authors.initials: PM
authors.lastname: Hammoudi
authors.affiliation: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 Rue Michel-Servet, CH-1211, Geneva 4, Switzerland.
authors.forename: Natacha
authors.initials: N
authors.lastname: Klages
authors.affiliation: Helmholtz Centre for Infection Research, Notkestrasse 85, Hamburg 22607, Germany German Electron Synchrotron (DESY), Notkestrasse 85, Hamburg 22607, Germany Department of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen 5009, Norway.
authors.forename: Juha Pekka
authors.initials: JP
authors.lastname: Kallio
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5400, Oulu 90014, Finland Helmholtz Centre for Infection Research, Notkestrasse 85, Hamburg 22607, Germany German Electron Synchrotron (DESY), Notkestrasse 85, Hamburg 22607, Germany Department of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen 5009, Norway.
authors.forename: Inari
authors.initials: I
authors.lastname: Kursula
authors.affiliation: Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 Rue Michel-Servet, CH-1211, Geneva 4, Switzerland dominique.soldati-favre@unige.ch.
authors.forename: Dominique
authors.initials: D
authors.lastname: Soldati-Favre
mesh_terms: D000595:Amino Acid Sequence; D051186:Armadillo Domain Proteins / Q000737:chemistry / Q000502:physiology*; D017124:Conserved Sequence; D008958:Models, Molecular; D015388:Organelles / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry / Q000502:physiology*; D014122:Toxoplasma / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D051186:Armadillo Domain Proteins; D015800:Protozoan Proteins
keywords: Apicomplexa; Armadillo repeat; Rhoptry organelle; Toxoplasma gondii