DOC2B, C2 Domains, and Calcium: A Tale of Intricate Interactions
DOC2B, C2 Domains, and Calcium: A Tale of Intricate Interactions
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DOI：
10.1007/s12035-009-8094-8
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发表时间：
2010-02-01
影响因子：
5.1
通讯作者：
Ashery, Uri
中科院分区：
文献类型：
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作者：
Friedrich, Reut;Yeheskel, Adva;Ashery, Uri
Ca+2依赖性胞吐作用涉及囊泡对接、引发、融合和再循环。这一过程由大量突触蛋白执行和调节，并取决于适当的蛋白质-蛋白质和蛋白质-脂质相互作用。双C2结构域（DOC 2）是在用C2探针筛选DNA文库时发现的由三种异构体组成的蛋白家族。DOC 2有三个结构域：Munc 13相互作用结构域和串联C2（命名为C2 A和C2B），由短极性接头连接。C2结构域以Ca 2+依赖性方式结合磷脂。这篇综述主要集中在广泛表达的异构体DOC 2B。串联C2蛋白家族在小鼠中的序列比对显示rabphilin-3A和DOC 2B蛋白之间的高度同源性（81%）。我们基于具有和不具有钙的rabphilin-3A的晶体结构创建了DOC 2B的C2 A的结构模型，并发现DOC 2B的钙结合环在钙结合时移动，使得其C2 A能够有效地穿透质膜。在这里，我们讨论了DOC 2B生物信息学模型及其功能之间的潜在关系，并提出了一个可能的工作模型，其与其他蛋白质的胞吐机制，包括Munc 13，Munc 18，和syntaxin的相互作用。
Ca+2-dependent exocytosis involves vesicle docking, priming, fusion, and recycling. This process is performed and regulated by a vast number of synaptic proteins and depends on proper protein-protein and protein- lipid interactions. Double C2 domain (DOC2) is a protein family of three isoforms found while screening DNA libraries with a C2 probe. DOC2 has three domains: the Munc13-interacting domain and tandem C2s (designated C2A and C2B) connected by a short polar linker. The C2 domain binds phospholipids in a Ca2+-dependent manner. This review focuses on the ubiquitously expressed isoform DOC2B. Sequence alignment of the tandem C2 protein family in mouse revealed high homology (81%) between rabphilin-3A and DOC2B proteins. We created a structural model of DOC2B's C2A based on the crystal structure of rabphilin-3A with and without calcium and found that the calcium-binding loops of DOC2B move upon calcium binding, enabling efficient plasma membrane penetration of its C2A. Here, we discuss the potential relation between the DOC2B bioinformatical model and its function and suggest a possible working model for its interaction with other proteins of the exocytotic machinery, including Munc13, Munc18, and syntaxin.