Yu Jong W, Mendrola Jeannine M, Audhya Anjon, Singh Shaneen, Keleti David, DeWald Daryll B, Murray Diana, Emr Scott D, Lemmon Mark A
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 USA.
Mol Cell. 2004 Mar 12;13(5):677-88. doi: 10.1016/s1097-2765(04)00083-8.
Pleckstrin homology (PH) domains are small protein modules known for their ability to bind phosphoinositides and to drive membrane recruitment of their host proteins. We investigated phosphoinositide binding (in vitro and in vivo) and subcellular localization, and we modeled the electrostatic properties for all 33 PH domains encoded in the S. cerevisiae genome. Only one PH domain (from Num1p) binds phosphoinositides with high affinity and specificity. Six bind phosphoinositides with moderate affinity and little specificity and are membrane targeted in a phosphoinositide-dependent manner. Although all of the remaining 26 yeast PH domains bind phosphoinositides very weakly or not at all, three were nonetheless efficiently membrane targeted. Our proteome-wide analysis argues that membrane targeting is important for only approximately 30% of yeast PH domains and is defined by binding to both phosphoinositides and other targets. These findings have significant implications for understanding the function of proteins that contain this common domain.
普列克底物蛋白同源（PH）结构域是一种小的蛋白质模块，以其结合磷酸肌醇以及驱动宿主蛋白募集到膜上的能力而闻名。我们研究了磷酸肌醇结合（体外和体内）及亚细胞定位，并对酿酒酵母基因组中编码的所有33个PH结构域的静电特性进行了建模。只有一个PH结构域（来自Num1p）以高亲和力和特异性结合磷酸肌醇。六个以中等亲和力和低特异性结合磷酸肌醇，并以磷酸肌醇依赖性方式定位于膜上。尽管其余26个酵母PH结构域与磷酸肌醇的结合非常弱或根本不结合，但其中三个仍能有效地定位于膜上。我们的全蛋白质组分析表明，膜定位仅对约30%的酵母PH结构域很重要，并且是通过与磷酸肌醇和其他靶点结合来定义的。这些发现对于理解含有这个常见结构域的蛋白质的功能具有重要意义。
