Cytoplasmic activation/proliferation‐associated protein (Caprin) proteins assume diverse functions in many important biological processes, including synaptic plasticity, stress response, innate immune response, and cellular proliferation. The Caprin family members are characterized by the presence of a highly conserved homologous region (HR1) at the N‐terminus and arginine‐glycine‐rich (RGG) boxes at the C‐terminus. We had previously determined the crystal structures of human Caprin‐1 and Caprin‐2 fragments corresponding to the C‐terminal 2/3 of HR1. Both fragments adopt homodimeric structures. Based on sequence conservation, we speculated that all Caprin proteins should have similar homodimeric structures. Here we report the crystal structure of a fragment (residues 187‐309) of Drosophila melanogaster Caprin (dCaprin). The dCaprin fragment adopts an all α‐helical fold which self‐associates to form a homodimer. The overall dCaprin homodimeric structure is similar to the Caprin‐1 and Caprin‐2 homodimeric structures. Most of the amino acids residues mediating homodimerization in the three structures are conserved among all Caprin family members. These structural and sequence data suggest that homodimerization through a conserved dimerization domain is a common structural feature of the Caprin protein family. The dimeric structures may also be involved in interaction with Caprin partners. Dimer formation creates a V‐shape concave surface that may serve as a protein binding groove. The concave surfaces in Caprin‐1, Caprin‐2, and dCaprin should have different and specific binding partners due to the large difference in electrostatic potentials. We propose the existence of a multi‐functional domain in Caprin proteins, which not only mediate homodimerization but also involve in interaction with specific Caprin partners.

中文翻译：

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果蝇山羊的 123 个氨基酸二聚化结构域的晶体结构。

细胞质激活/增殖相关蛋白 (Caprin) 蛋白在许多重要的生物过程中承担多种功能，包括突触可塑性、应激反应、先天免疫反应和细胞增殖。Caprin 家族成员的特点是 N 端存在高度保守的同源区 (HR1)，C 端存在富含精氨酸-甘氨酸 (RGG) 的框。我们之前已经确定了对应于 HR1 C 端 2/3 的人 Caprin-1 和 Caprin-2 片段的晶体结构。两个片段均采用同源二聚体结构。基于序列保守性，我们推测所有 Caprin 蛋白都应该具有相似的同源二聚体结构。在这里，我们报告了黑腹果蝇片段（残基 187-309）的晶体结构卡普林 (dCaprin)。dCaprin 片段采用全 α 螺旋折叠，自缔合形成同源二聚体。整体 dCaprin 同二聚体结构类似于 Caprin-1 和 Caprin-2 同二聚体结构。三种结构中介导同源二聚化的大多数氨基酸残基在所有 Caprin 家族成员中都是保守的。这些结构和序列数据表明，通过保守二聚化结构域的同源二聚化是 Caprin 蛋白家族的共同结构特征。二聚体结构也可能参与与 Caprin 伙伴的相互作用。二聚体的形成产生了一个 V 形凹面，可以作为蛋白质结合槽。由于静电势的巨大差异，Caprin-1、Caprin-2 和 dCaprin 中的凹面应具有不同且特定的结合伙伴。