Crystal structure of the Bruton's tyrosine kinase PH domain with phosphatidylinositol.
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.
Murayama
Kazutaka
K
Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
Kato-Murayama
Miyuki
M
Mishima
Chiemi
C
Akasaka
Ryogo
R
Shirouzu
Mikako
M
Fukui
Yasuhisa
Y
Yokoyama
Shigeyuki
S
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*
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