Crystal structure of the Bruton's tyrosine kinase PH domain with phosphatidylinositol

Kazutaka Murayama; Miyuki Kato-Murayama; Chiemi Mishima; Ryogo Akasaka; Mikako Shirouzu; Yasuhisa Fukui; Shigeyuki Yokoyama

doi:10.1016/j.bbrc.2008.09.055

Crystal structure of the Bruton's tyrosine kinase PH domain with phosphatidylinositol

Kazutaka Murayama, Miyuki Kato-Murayama, Chiemi Mishima, Ryogo Akasaka, Mikako Shirouzu, Yasuhisa Fukui, Shigeyuki Yokoyama

MEN - Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	23-28
Number of pages	6
Journal	Biochemical and biophysical research communications
Volume	377
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2008.09.055
Publication status	Published - 2008 Dec 5

Keywords

Complex structure
Dimerization
Membrane targeting
Phosphatidylinositol
Pleckstrin homology domain

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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Crystal structure of the Bruton's tyrosine kinase PH domain with phosphatidylinositol. / Murayama, Kazutaka; Kato-Murayama, Miyuki; Mishima, Chiemi; Akasaka, Ryogo; Shirouzu, Mikako; Fukui, Yasuhisa; Yokoyama, Shigeyuki.

In: Biochemical and biophysical research communications, Vol. 377, No. 1, 05.12.2008, p. 23-28.

Research output: Contribution to journal › Article › peer-review

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AU - Mishima, Chiemi

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AU - Shirouzu, Mikako

AU - Fukui, Yasuhisa

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