Protein kinase C (PKC) family members are multi‐domain proteins whose function is exquisitely tuned by interdomain interactions that control the spatiotemporal dynamics of their signaling. Despite extensive mechanistic studies on this family of enzymes, no structure of a full‐length enzyme that includes all domains has been solved. Here, we take into account the biochemical mechanisms that control autoinhibition, the properties of each individual domain, and previous structural studies to propose a unifying model for the general architecture of PKC family members. This model shows how the C2 domains of conventional and novel PKC isozymes, which have different topologies and different positions in the primary structure, can occupy the same position in the tertiary structure of the kinase. This common architecture of conventional and novel PKC isozymes provides a framework for understanding how disease‐associated mutations impair PKC function.

中文翻译：

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假设：传统和新型蛋白激酶 C 同工酶的域结构统一模型

蛋白激酶 C (PKC) 家族成员是多域蛋白质，其功能通过域间相互作用进行精细调整，域间相互作用控制其信号的时空动态。尽管对该酶家族进行了广泛的机理研究，但尚未解决包含所有结构域的全长酶的结构。在这里，我们考虑了控制自动抑制的生化机制、每个单独域的特性和以前的结构研究，为 PKC 家族成员的一般结构提出了一个统一模型。该模型显示了常规和新型 PKC 同工酶的 C2 结构域如何在激酶的三级结构中占据相同的位置，它们在一级结构中具有不同的拓扑结构和不同的位置。