Genomic structure of the human complement protein C8 gamma: homology to the lipocalin gene family.
Genomic structure of the human complement protein C8 gamma: homology to the lipocalin gene family.
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DOI：
10.1021/bi00183a020
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发表时间：
1994-05
期刊：
影响因子：
2.9
通讯作者：
Kenneth M. Kaufman;J. Sodetz
中科院分区：
文献类型：
--
作者：
Kenneth M. Kaufman;J. Sodetz
人 C8 是五种补体成分（C5b、C6、C7、C8、C9）之一，它们相互作用在靶细胞上形成溶细胞 C5b-9 复合物。它包含三个亚基（C8 α、C8 β、C8 γ），它们由不同的基因编码。与补体系统的其他蛋白质相比，C8 γ 的不同寻常之处在于它在结构上与任何其他成分均不相关，也不具有明显的功能。基于微弱但显着的序列相似性，它被认为是广泛分布的脂质运载蛋白家族的成员，可结合和运输小的疏水性配体。在这项研究中，人类 C8 γ 基因已被表征并发现包含七个外显子，跨度约为 1.8 kb。使用S1核酸酶和锚定PCR来鉴定转录起始位点。该位点之前是假定的调控元件，其中包括两个 SP1 结合位点、几个糖皮质激素反应元件和两个 SV40 增强子核心共有序列。与其他脂质运载蛋白基因的比较揭示了外显子数量、长度和相位的非常密切的相关性。还观察到外显子边界的密切对应，这表明 C8 γ 包含相同的离散结构元件，这些元件定义了脂质运载蛋白的特征性 β 桶形状。这些结果证实，C8 γ 确实与脂质运载蛋白家族有祖先关系，并增强了其在补体系统中的作用是结合尚未鉴定的配体的可能性。
Human C8 is one of five complement components (C5b, C6, C7, C8, C9) that interact to form the cytolytic C5b-9 complex on target cells. It contains three subunits (C8 alpha, C8 beta, C8 gamma) which are encoded in separate genes. In relation to other proteins of the complement system, C8 gamma is unusual in that it is not structurally related to any other component nor does it have an obvious function. Based on weak but significant sequence similarity, it is proposed to be a member of the lipocalin family of widely distributed proteins that bind and transport small hydrophobic ligands. In this study, the human C8 gamma gene has been characterized and found to contain seven exons spanning approximately 1.8 kb. S1 nuclease and anchored PCR were used to identify the transcription initiation site. This site is preceded by putative regulatory elements that include two SP1 binding sites, several glucocorticoid response elements, and two SV40 enhancer core consensus sequences. A comparison to genes of other lipocalins reveals a remarkably close correlation in exon number, lengths, and phases. A close correspondence in exon boundaries is also observed and suggests that C8 gamma contains the same discrete structural elements that define the characteristic beta-barrel shape of the lipocalins. These results establish that C8 gamma is indeed ancestrally related to the lipocalin family and strengthens the likelihood that its role in the complement system is to bind an as yet unidentified ligand.