title: The role of palmitoylation for protein recruitment to the inner membrane complex of the malaria parasite.
abstract: To survive and persist within its human host, the malaria parasite Plasmodium falciparum utilizes a battery of lineage-specific innovations to invade and multiply in human erythrocytes. With central roles in invasion and cytokinesis, the inner membrane complex, a Golgi-derived double membrane structure underlying the plasma membrane of the parasite, represents a unique and unifying structure characteristic to all organisms belonging to a large phylogenetic group called Alveolata. More than 30 structurally and phylogenetically distinct proteins are embedded in the IMC, where a portion of these proteins displays N-terminal acylation motifs. Although N-terminal myristoylation is catalyzed co-translationally within the cytoplasm of the parasite, palmitoylation takes place at membranes and is mediated by palmitoyl acyltransferases (PATs). Here, we identify a PAT (PfDHHC1) that is exclusively localized to the IMC. Systematic phylogenetic analysis of the alveolate PAT family reveals PfDHHC1 to be a member of a highly conserved, apicomplexan-specific clade of PATs. We show that during schizogony this enzyme has an identical distribution like two dual-acylated, IMC-localized proteins (PfISP1 and PfISP3). We used these proteins to probe into specific sequence requirements for IMC-specific membrane recruitment and their interaction with differentially localized PATs of the parasite.
authors.affiliation: From the M. G. DeGroote Institute for Infectious Disease Research, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Johanna
authors.initials: J
authors.lastname: Wetzel
authors.affiliation: From the M. G. DeGroote Institute for Infectious Disease Research, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Susann
authors.initials: S
authors.lastname: Herrmann
authors.affiliation: the Program in Molecular Structure and Function, Hospital for Sick Children, and Departments of Biochemistry and Molecular Genetics, University of Toronto, Toronto, Ontario M5G 0A4, Canada.
authors.forename: Lakshmipuram Seshadri
authors.initials: LS
authors.lastname: Swapna
authors.affiliation: From the M. G. DeGroote Institute for Infectious Disease Research, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Dhaneswar
authors.initials: D
authors.lastname: Prusty
authors.affiliation: the Department of Biology/Chemistry, Biochemistry Section, University of Osnabrück, 49076 Osnabrück, Germany.
authors.forename: Arun T
authors.initials: AT
authors.lastname: John Peter
authors.affiliation: the Bernhard-Nocht-Institute for Tropical Medicine, 20359 Hamburg, Germany, and.
authors.forename: Maya
authors.initials: M
authors.lastname: Kono
authors.affiliation: From the M. G. DeGroote Institute for Infectious Disease Research, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Sidharth
authors.initials: S
authors.lastname: Saini
authors.affiliation: From the M. G. DeGroote Institute for Infectious Disease Research, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Nellimarla
authors.affiliation: From the M. G. DeGroote Institute for Infectious Disease Research, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Tatianna Wai Ying
authors.initials: TW
authors.lastname: Wong
authors.affiliation: From the M. G. DeGroote Institute for Infectious Disease Research, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada, the Bernhard-Nocht-Institute for Tropical Medicine, 20359 Hamburg, Germany, and.
authors.forename: Louisa
authors.initials: L
authors.lastname: Wilcke
authors.affiliation: From the M. G. DeGroote Institute for Infectious Disease Research, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Olivia
authors.initials: O
authors.lastname: Ramsay
authors.affiliation: From the M. G. DeGroote Institute for Infectious Disease Research, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Ana
authors.initials: A
authors.lastname: Cabrera
authors.affiliation: the Bernhard-Nocht-Institute for Tropical Medicine, 20359 Hamburg, Germany, and.
authors.forename: Laura
authors.initials: L
authors.lastname: Biller
authors.affiliation: From the M. G. DeGroote Institute for Infectious Disease Research, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada, the Bernhard-Nocht-Institute for Tropical Medicine, 20359 Hamburg, Germany, and.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Heincke
authors.affiliation: From the M. G. DeGroote Institute for Infectious Disease Research, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Mossman
authors.affiliation: the Bernhard-Nocht-Institute for Tropical Medicine, 20359 Hamburg, Germany, and.
authors.forename: Tobias
authors.initials: T
authors.lastname: Spielmann
authors.affiliation: the Department of Biology/Chemistry, Biochemistry Section, University of Osnabrück, 49076 Osnabrück, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Ungermann
authors.affiliation: the Program in Molecular Structure and Function, Hospital for Sick Children, and Departments of Biochemistry and Molecular Genetics, University of Toronto, Toronto, Ontario M5G 0A4, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Parkinson
authors.affiliation: From the M. G. DeGroote Institute for Infectious Disease Research, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada, the Bernhard-Nocht-Institute for Tropical Medicine, 20359 Hamburg, Germany, and the Center for Structural Systems Biology, 22607 Hamburg, Germany tgilber@mcmaster.ca.
authors.forename: Tim W
authors.initials: TW
authors.lastname: Gilberger
mesh_terms: D000199:Actins / Q000737:chemistry; D000217:Acyltransferases / Q000378:metabolism*; D001710:Biotin / Q000737:chemistry; D002384:Catalysis; D002462:Cell Membrane / Q000378:metabolism*; D004252:DNA Mutational Analysis; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008288:Malaria / Q000469:parasitology; D008565:Membrane Proteins / Q000378:metabolism*; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015800:Protozoan Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D008565:Membrane Proteins; D015800:Protozoan Proteins; D049452:Green Fluorescent Proteins; D001710:Biotin; D000217:Acyltransferases
keywords: Inner Membrane Complex; Malaria; Membrane Trafficking; Palmitoyl Acyltransferase; Phylogenetics; Plasmodium; Protein Acylation