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.

Institute of Microbiology AS CR v v i Videnska 1083 Prague Czech Republic Department of Biochemistry Faculty of Science Charles University Prague Hlavova 8 Prague Czech Republic

Institute of Organic Chemistry and Biochemistry AS CR v v i Flemingovo nam 2 16610 Prague 6 Czech Republic

Laboratory of Biomolecular Research Department of Biology and Chemistry Paul Scherrer Institute 5232 Villigen PSI Switzerland

Section on Molecular Signal Transduction Program for Developmental Neuroscience NICHD NIH Bethesda MD 20892 USA

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$a Klima, Martin $u Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.

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$a Structural insights and in vitro reconstitution of membrane targeting and activation of human PI4KB by the ACBD3 protein / $c M. Klima, DJ. Tóth, R. Hexnerova, A. Baumlova, D. Chalupska, J. Tykvart, L. Rezabkova, N. Sengupta, P. Man, A. Dubankova, J. Humpolickova, R. Nencka, V. Veverka, T. Balla, E. Boura,

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$a 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.

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$a Tóth, Dániel J $u Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD, NIH, Bethesda, MD 20892, USA.

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$a Hexnerova, Rozalie $u Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.

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$a Baumlova, Adriana $u Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.

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$a Chalupska, Dominika $u Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.

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$a Tykvart, Jan $u Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.

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$a Rezabkova, Lenka $u Laboratory of Biomolecular Research, Department of Biology and Chemistry, Paul Scherrer Institute, 5232, Villigen PSI, Switzerland.

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$a Sengupta, Nivedita $u Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD, NIH, Bethesda, MD 20892, USA.

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$a Man, Petr $u 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.

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$a Dubánková, Anna $u Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic. $7 xx0318260

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$a Humpolickova, Jana $u Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.

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$a Balla, Tamas $u Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD, NIH, Bethesda, MD 20892, USA.

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$a Boura, Evzen $u Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.

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