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首页> 外文期刊>Frontiers in Immunology >Evolutionary Origin of the P2X7 C-ter Region: Capture of an Ancient Ballast Domain by a P2X4-Like Gene in Ancient Jawed Vertebrates
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Evolutionary Origin of the P2X7 C-ter Region: Capture of an Ancient Ballast Domain by a P2X4-Like Gene in Ancient Jawed Vertebrates

机译：P2X7 C-TER区域的进化起源：在古代下颚脊椎动物中的P2x4样基因捕获古老的镇流器域

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摘要

P2X purinergic receptors are extracellular ATP-gated ion channel receptors present on the cell plasma membrane. P2X receptors have been found in Metazoa, fungi, amoebas, and in plants. In mammals, P2X7 is expressed by a large number of cell types and is involved in inflammation and immunity. Remarkably, P2X7 does not desensitize as other P2X do, a feature linked to a “C-cysteine anchor” intra-cytoplasmic motif encoded by exon 11. Another specific feature of P2X7 is its C-terminal cytoplasmic ballast domain (exon 13) which contains a zinc (Zn) coordinating cysteine motif and a GDP-binding region. To determine the origin of P2X7, we analyzed and compared sequences and protein motifs of the C-terminal intra-cytoplasmic region across all main groups of Metazoa. We identified proteins with typical ballast domains, sharing a remarkably conserved Zn-coordinating cysteine motif. Apart from vertebrates, these ballast domains were not associated with a typical P2X architecture. These results strongly suggest that P2X7 resulted from the fusion of a P2X gene, highly similar to P2X4, with an exon encoding a ballast domain. Our work brings new evidence on the origin of the P2X7 purinergic receptor and identifies the Zn-coordinating cysteine domain as the fundamental feature of the ancient ballast fold.
机译：P2X嘌呤能受体是存在于细胞质膜上的细胞外ATP腺门通道受体。 P2x受体已在Metazoa，真菌，Amoebas和植物中发现。在哺乳动物中，P2X7由大量细胞类型表达，并且涉及炎症和免疫。值得注意的是，P2X7不作为其他P2x脱敏，将由外显子11编码的“C-Cysteine锚定”内胞质上的细胞质上的特征。P2X7的另一个特征是其C末端细胞质压域（外显子13）。锌（Zn）配位半胱氨酸基序和GDP结合区域。为了确定P2X7的起源，我们在所有主要组的Metazoa中分析和比较了C末端内细胞质区域的序列和蛋白质基序。我们鉴定出具有典型镇流器结构域的蛋白质，共用显着保守的Zn协调半胱氨酸基序。除了脊椎动物外，这些镇流器域与典型的P2x架构无关。这些结果强烈建议P2X7由P2x基因的融合产生高度相似的P2X4，具有编码镇流器结构域的外显子。我们的作品为P2X7嘌呤能受体的起源带来了新的证据，并将Zn协调半胱氨酸结构域鉴定为古老镇流器折叠的基本特征。

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