The PCI domains are "winged" HEAT domains.

The PCI domains are "winged" HEAT domains.
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DOI:
10.1371/journal.pone.0268664
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发表时间:
2022
期刊:
影响因子:
3.7
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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HEAT结构域是由四个或更多个发夹组成的螺旋发夹重复结构域家族。HEAT来源于四个家族成员的名称:亨廷顿蛋白、真核翻译延伸因子3(eEF 3)、蛋白磷酸酶2调节A亚基(PP 2A)和雷帕霉素机制靶点(mTOR)。含HEAT结构域的蛋白质在广泛的细胞过程中发挥作用,例如蛋白质合成、核转运和代谢以及细胞信号传导。PCI结构域是一组相关的螺旋发夹结构域,在它们的C-末端具有“翼状螺旋”(WH)亚结构域,其负责与其他PCI结构域形成多亚基复合物。这个名字来源于复合物,其中发现了这些结构域:26 S蛋白酶体“盖子”调节亚复合物,COP 9信号体(CSN)和真核翻译起始因子3(eIF 3)。我们注意到,在使用HEAT结构域的结构相似性搜索中,有时PCI结构域出现在其他HEAT结构域之前的搜索结果中,这表明PCI结构域可能是HEAT结构域家族的成员,而不是像目前认为的那样是一个相关但独立的组。在这里,我们报告广泛的结构相似性分析的热和PCI域,无论是内部和两组蛋白质之间。我们提出的证据表明,PCI域作为一个组有更大的结构相似性与个别组的热域比一些热域组之间的其他。因此,我们的研究结果表明,PCI域已经从获得WH子域的HEAT域演变而来。WH亚结构域又介导自缔合成多亚基复合物,其最终进化成蛋白酶体lid/CSN/eIF 3的共同祖先。
The HEAT domains are a family of helical hairpin repeat domains, composed of four or more hairpins. HEAT is derived from the names of four family members: huntingtin, eukaryotic translation elongation factor 3 (eEF3), protein phosphatase 2 regulatory A subunit (PP2A), and mechanistic target of rapamycin (mTOR). HEAT domain-containing proteins play roles in a wide range of cellular processes, such as protein synthesis, nuclear transport and metabolism, and cell signaling. The PCI domains are a related group of helical hairpin domains, with a “winged-helix” (WH) subdomain at their C-terminus, which is responsible for multi-subunit complex formation with other PCI domains. The name is derived from the complexes, where these domains are found: the 26S Proteasome “lid” regulatory subcomplex, the COP9 signalosome (CSN), and eukaryotic translation initiation factor 3 (eIF3). We noted that in structure similarity searches using HEAT domains, sometimes PCI domains appeared in the search results ahead of other HEAT domains, which indicated that the PCI domains could be members of the HEAT domain family, and not a related but separate group, as currently thought. Here, we report extensive structure similarity analysis of HEAT and PCI domains, both within and between the two groups of proteins. We present evidence that the PCI domains as a group have greater structural similarity with individual groups of HEAT domains than some of the HEAT domain groups have among each other. Therefore, our results indicate that the PCI domains have evolved from a HEAT domain that acquired a WH subdomain. The WH subdomain in turn mediated self-association into a multi-subunit complex, which eventually evolved into the common ancestor of the Proteasome lid/CSN/eIF3.
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