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PICK1蛋白是一个从线虫到人都高度保守膜周蛋白,在多种组织中表达,尤以脑和睾丸的表达最高。在细胞内,PICK1定位于核周区和诸如神经突触的特化细胞结构中。PICK1蛋白含一个PDZ结构域和一个BAR结构域,PDZ结构域能和许多膜蛋白结合,而BAR结构域能与脂质分子(主要为磷酸肌醇)相结合,通过这种机制PICK1可调节相关蛋白的亚细胞定位和膜表达。由于各蛋白与PICK1相互作用的PDZ结合基序不同,可利用与特定蛋白结合基序相同的PDZ结合多肽竞争性地结合PDZ结构域,特异性地阻断该蛋白的作用,从而特异性地增强或减弱PICK1在某组织中的作用,为PICK1的临床应用提供了药理基础。
PICK1 protein is a highly conserved perimembranous protein from nematodes to humans and is expressed in a variety of tissues, especially in the brain and testes. Within the cell, PICK1 is localized in the perinuclear zone and in specialized cellular structures such as neuronal synapses. The PICK1 protein contains a PDZ domain and a BAR domain. The PDZ domain binds to many membrane proteins. The BAR domain binds to lipid molecules, mainly phosphoinositides, by which PICK1 regulates the association Subcellular localization of proteins and membrane expression. Due to the different PDZ binding motifs of each protein interacting with PICK1, PDZ binding polypeptides that bind to the same PDZ binding motif as a particular protein binding motif can be used to competitively bind to the PDZ domain to specifically block the action of the protein and thereby specifically enhance Or weaken the role of PICK1 in a tissue, which provides a pharmacological basis for the clinical application of PICK1.