Lemmon Mark A, Ferguson Kathryn M, Abrams Charles S
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 809C Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104-6059, USA.
FEBS Lett. 2002 Feb 20;513(1):71-6. doi: 10.1016/s0014-5793(01)03243-4.
Pleckstrin homology (PH) domains are 100-120 amino acid protein modules best known for their ability to bind phosphoinositides. All possess an identical core beta-sandwich fold and display marked electrostatic sidedness. The binding site for phosphoinositides lies in the center of the positively charged face. In some cases this binding site is well defined, allowing highly specific and strong ligand binding. In several of these cases the PH domains specifically recognize 3-phosphorylated phosphoinositides, allowing them to drive membrane recruitment in response to phosphatidylinositol 3-kinase activation. Examples of these PH domain-containing proteins include certain Dbl family guanine nucleotide exchange factors, protein kinase B, PhdA, and pleckstrin-2. PH domain-mediated membrane recruitment of these proteins contributes to regulated actin assembly and cell polarization. Many other PH domain-containing cytoskeletal proteins, such as spectrin, have PH domains that bind weakly, and to all phosphoinositides. In these cases, the individual phosphoinositide interactions may not be sufficient for membrane association, but appear to require self-assembly of their host protein and/or cooperation with other anchoring motifs within the same molecule to drive membrane attachment.
普列克底物蛋白同源（PH）结构域是由100 - 120个氨基酸组成的蛋白质模块，以其结合磷酸肌醇的能力而闻名。所有PH结构域都具有相同的核心β - 折叠结构，并表现出明显的静电方向性。磷酸肌醇的结合位点位于带正电荷面的中心。在某些情况下，该结合位点定义明确，允许高度特异性和强的配体结合。在其中一些情况下，PH结构域特异性识别3 - 磷酸化的磷酸肌醇，使其能够响应磷脂酰肌醇3 - 激酶激活而驱动膜募集。这些含PH结构域的蛋白质的例子包括某些Dbl家族鸟嘌呤核苷酸交换因子、蛋白激酶B、PhdA和普列克底物蛋白 - 2。这些蛋白质由PH结构域介导的膜募集有助于调节肌动蛋白组装和细胞极化。许多其他含PH结构域的细胞骨架蛋白，如血影蛋白，其PH结构域结合较弱，且能结合所有磷酸肌醇。在这些情况下，单个磷酸肌醇相互作用可能不足以实现膜结合，但似乎需要其宿主蛋白的自组装和/或与同一分子内的其他锚定基序协同作用来驱动膜附着。
