title: Crystal structure of the Bruton's tyrosine kinase PH domain with phosphatidylinositol.
abstract: Bruton's tyrosine kinase (Btk) of the Tec family possesses a Pleckstrin homology (PH) domain, which is responsible for plasma membrane targeting. In this study, the crystal structure of the Btk PH domain in complex with dibutylyl-phosphatidylinositol-3,4,5-triphosphate was determined. The structure revealed that the Btk PH domain forms a homodimer and that each molecule binds phosphatidylinositol in the binding pocket. The side chain of Lys18 within a Btk-specific insertion in the beta1-beta2 loop is able to form a hydrogen bond with the diacylglycerol moiety of phosphatidylinositol. The other Btk-specific insertion in the beta5-beta6 loop constitutes the dimerization interface. Thus, the modes of phosphatidylinositol recognition and Btk PH domain dimerization are distinct from those of other PH domains.
authors.affiliation: Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Murayama
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kato-Murayama
authors.forename: Chiemi
authors.initials: C
authors.lastname: Mishima
authors.forename: Ryogo
authors.initials: R
authors.lastname: Akasaka
authors.forename: Mikako
authors.initials: M
authors.lastname: Shirouzu
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fukui
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000595:Amino Acid Sequence; D001798:Blood Proteins / Q000737:chemistry; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008969:Molecular Sequence Data; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry*; D010750:Phosphoproteins / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry*
chemical_list: D001798:Blood Proteins; D018129:Phosphatidylinositol Phosphates; D010750:Phosphoproteins; C060974:phosphatidylinositol 3,4,5-triphosphate; C039077:platelet protein P47; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human