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
N1 - Funding Information:
This work was supported by Special Coordination Funds for Promoting Science and Technology, and the RIKEN Structure Genomics/Proteomics Initiative in the National Project on Protein Structural and Functional Analyses, Ministry of Education, Culture, Sports, Science and Technology. We thank Takako Fujimoto and Dr. Sumiko Gomi for their technical assistance in protein expressions.
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 -