TY - JOUR
T1 - Crystal structure of the Bruton's tyrosine kinase PH domain with phosphatidylinositol
AU - Murayama, Kazutaka
AU - Kato-Murayama, Miyuki
AU - Mishima, Chiemi
AU - Akasaka, Ryogo
AU - Shirouzu, Mikako
AU - Fukui, Yasuhisa
AU - Yokoyama, Shigeyuki
PY - 2008/12/5
Y1 - 2008/12/5
N2 - 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 β1-β2 loop is able to form a hydrogen bond with the diacylglycerol moiety of phosphatidylinositol. The other Btk-specific insertion in the β5-β6 loop constitutes the dimerization interface. Thus, the modes of phosphatidylinositol recognition and Btk PH domain dimerization are distinct from those of other PH domains.
AB - 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 β1-β2 loop is able to form a hydrogen bond with the diacylglycerol moiety of phosphatidylinositol. The other Btk-specific insertion in the β5-β6 loop constitutes the dimerization interface. Thus, the modes of phosphatidylinositol recognition and Btk PH domain dimerization are distinct from those of other PH domains.
KW - Complex structure
KW - Dimerization
KW - Membrane targeting
KW - Phosphatidylinositol
KW - Pleckstrin homology domain
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U2 - 10.1016/j.bbrc.2008.09.055
DO - 10.1016/j.bbrc.2008.09.055
M3 - Article
C2 - 18809383
AN - SCOPUS:54449091168
VL - 377
SP - 23
EP - 28
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -