title: Structural insights and in vitro reconstitution of membrane targeting and activation of human PI4KB by the ACBD3 protein.
abstract: Phosphatidylinositol 4-kinase beta (PI4KB) is one of four human PI4K enzymes that generate phosphatidylinositol 4-phosphate (PI4P), a minor but essential regulatory lipid found in all eukaryotic cells. To convert their lipid substrates, PI4Ks must be recruited to the correct membrane compartment. PI4KB is critical for the maintenance of the Golgi and trans Golgi network (TGN) PI4P pools, however, the actual targeting mechanism of PI4KB to the Golgi and TGN membranes is unknown. Here, we present an NMR structure of the complex of PI4KB and its interacting partner, Golgi adaptor protein acyl-coenzyme A binding domain containing protein 3 (ACBD3). We show that ACBD3 is capable of recruiting PI4KB to membranes both in vitro and in vivo, and that membrane recruitment of PI4KB by ACBD3 increases its enzymatic activity and that the ACBD3:PI4KB complex formation is essential for proper function of the Golgi.
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Klima
authors.affiliation: Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD, NIH, Bethesda, MD 20892, USA.
authors.forename: Dániel J
authors.initials: DJ
authors.lastname: Tóth
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.
authors.forename: Rozalie
authors.initials: R
authors.lastname: Hexnerova
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.
authors.forename: Adriana
authors.initials: A
authors.lastname: Baumlova
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.
authors.forename: Dominika
authors.initials: D
authors.lastname: Chalupska
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Tykvart
authors.affiliation: Laboratory of Biomolecular Research, Department of Biology and Chemistry, Paul Scherrer Institute, 5232, Villigen PSI, Switzerland.
authors.forename: Lenka
authors.initials: L
authors.lastname: Rezabkova
authors.affiliation: Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD, NIH, Bethesda, MD 20892, USA.
authors.forename: Nivedita
authors.initials: N
authors.lastname: Sengupta
authors.affiliation: Institute of Microbiology AS CR, v.v.i., Videnska 1083, Prague, Czech Republic.|Department of Biochemistry, Faculty of Science, Charles University in Prague, Hlavova 8, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Man
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Dubankova
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Humpolickova
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.
authors.forename: Radim
authors.initials: R
authors.lastname: Nencka
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.
authors.forename: Vaclav
authors.initials: V
authors.lastname: Veverka
authors.affiliation: Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD, NIH, Bethesda, MD 20892, USA.
authors.forename: Tamas
authors.initials: T
authors.lastname: Balla
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.
authors.forename: Evzen
authors.initials: E
authors.lastname: Boura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; D017853:Phosphotransferases (Alcohol Group Acceptor); C449459:ACBD3 protein, human; C037178:phosphatidylinositol 4-phosphate; C581087:PI4KB protein, human