普列克底物蛋白同源结构域区分3-磷酸肌醇的结构基础。
Structural basis for discrimination of 3-phosphoinositides by pleckstrin homology domains.
作者信息
Ferguson K M, Kavran J M, Sankaran V G, Fournier E, Isakoff S J, Skolnik E Y, Lemmon M A
机构信息
Department of Biochemistry and Biophysics and The Johnson Foundation, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
出版信息
Mol Cell. 2000 Aug;6(2):373-84. doi: 10.1016/s1097-2765(00)00037-x.
Pleckstrin homology (PH) domains are protein modules of around 120 amino acids found in many proteins involved in cellular signaling. Certain PH domains drive signal-dependent membrane recruitment of their host proteins by binding strongly and specifically to lipid second messengers produced by agonist-stimulated phosphoinositide 3-kinases (PI 3-Ks). We describe X-ray crystal structures of two different PH domains bound to Ins(1,3,4,5)P4, the head group of the major PI 3-K product PtdIns(3,4,5)P3. One of these PH domains (from Grp1) is PtdIns(3,4,5)P3 specific, while the other (from DAPP1/PHISH) binds strongly to both PtdIns(3,4,5)P3 and its 5'-dephosphorylation product, PtdIns(3,4)P2. Comparison of the two structures provides an explanation for the distinct phosphoinositide specificities of the two PH domains and allows us to predict the 3-phosphoinositide selectivity of uncharacterized PH domains.
普列克底物蛋白同源（PH）结构域是一种由约120个氨基酸组成的蛋白质模块，存在于许多参与细胞信号传导的蛋白质中。某些PH结构域通过与激动剂刺激的磷酸肌醇3激酶（PI 3-Ks）产生的脂质第二信使强烈且特异性结合，驱动其宿主蛋白的信号依赖性膜募集。我们描述了与Ins(1,3,4,5)P4结合的两种不同PH结构域的X射线晶体结构，Ins(1,3,4,5)P4是主要PI 3-K产物PtdIns(3,4,5)P3的头部基团。其中一个PH结构域（来自Grp1）对PtdIns(3,4,5)P3具有特异性，而另一个（来自DAPP1/PHISH）则与PtdIns(3,4,5)P3及其5'-去磷酸化产物PtdIns(3,4)P2都有很强的结合。两种结构的比较为两个PH结构域不同的磷酸肌醇特异性提供了解释，并使我们能够预测未表征的PH结构域对3-磷酸肌醇的选择性。
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