γ-glutamyl carboxylation:: An extracellular posttranslational modification that antedates the divergence of molluscs, arthropods, and chordates
γ-glutamyl carboxylation:: An extracellular posttranslational modification that antedates the divergence of molluscs, arthropods, and chordates
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DOI：
10.1073/pnas.022637099
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发表时间：
2002-02-05
影响因子：
11.1
通讯作者：
Olivera, BM
中科院分区：
文献类型：
--
作者：
Bandyopadhyay, PK;Garrett, JE;Olivera, BM
分泌蛋白中谷氨酸残基翻译后羧化为γ-羧基谷氨酸是由维生素K依赖性酶γ-谷氨酰羧化酶进行的。γ-羧基化一直被认为是脊椎动物的生化特化，对血液凝固至关重要。最近，一种γ-羧化酶被证明在果蝇中表达，尽管它的功能在这种生物体中仍然不确定。我们已经表征了海洋软体动物芋螺的γ-谷氨酰羧化酶的cDNA和基因组克隆，芋螺是唯一的非脊椎动物生物体，其含有γ-羧基谷氨酸的蛋白质已被生化和生理学表征。预测的氨基酸序列与果蝇和脊椎动物的酶具有高度的序列相似性。虽然γ-羧化酶是高度保守的，但芋螺和哺乳动物的酶具有不同的底物特异性。芋螺和人类γ-羧化酶的基因结构有着惊人的相似之处。在鉴定的10个芋螺内含子中，8个与人类酶中相应的内含子位置完全相同。内含子/外显子边界的这种显著的保守性揭示了富含内含子的γ-羧化酶存在于动物门的进化早期;尽管已经鉴定了哺乳动物和软体动物中需要这种细胞外修饰的专门适应，但γ-羧化的祖先功能和更广泛的生物学作用仍然需要定义。这些数据提出了一种可能性，即哺乳动物和软体动物基因中的大多数内含子都先于这些门的分歧。
The posttranslational,carboxylation of glutamate residues in secreted proteins to gamma-carboxyglutamate is carried out by the vitamin K-dependent enzyme gamma-glutamyl carboxylase. gamma-Carboxylation has long been thought to be a biochemical specialization of vertebrates, essential for blood clotting. Recently, a gamma-carboxylase was shown to be expressed in Drosophila, although its function remains undefined in this organism. We have characterized both cDNA and genomic clones for the gamma-glutamyl carboxylase from the marine mollusc, Conus, the only nonvertebrate organism for which gamma-carboxyglutamate-containing proteins have been biochemically and physiologically characterized. The predicted amino acid sequence has a high degree of sequence similarity to the Drosophila and vertebrate enzymes. Although gamma-carboxylases are highly conserved, the Conus and mammalian enzymes have divergent substrate specificity. There are striking parallels in the gene organization of Conus and human gamma-carboxylases. Of the 10 Conus introns identified, 8 are in precisely the same position as the corresponding introns in the human enzyme. This remarkable conservation of intron/exon boundaries reveals that an intron-rich gamma-carboxylase was present early in the evolution of the animal phyla; although specialized adaptations in mammals and molluscs that require this extracellular modification have been identified, the ancestral function(s) and wider biological roles of gamma-carboxylation still need to be defined. The data raise the possibility that most introns in the genes of both mammals and molluscs antedate the divergence of these phyla.