Globin X is a six-coordinate globin that reduces nitrite to nitric oxide in fish red blood cells
Globin X is a six-coordinate globin that reduces nitrite to nitric oxide in fish red blood cells
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DOI：
10.1073/pnas.1522670113
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发表时间：
2016-07-26
影响因子：
11.1
通讯作者：
Gladwin, Mark T.
中科院分区：
文献类型：
--
作者：
Corti, Paola;Xue, Jianmin;Gladwin, Mark T.
在不同生物体中发现新的珠蛋白，激发了人们对其进化功能的浓厚兴趣，而不仅仅是氧结合。球蛋白X(GBX)是一种发现于鱼类、两栖动物和爬行动物中的蛋白质，它起源于哺乳动物血红蛋白和肌红蛋白的共同祖先。与哺乳动物脑红蛋白一样，GBX最初在鱼类中被指定为神经性球蛋白，并显示出六配位的血红素构型，表明它参与细胞内的电子转移反应，而不是氧结合。在这里，我们报道，据我们所知，GBX是第一个六配位的珠蛋白，也是除血红蛋白外，在脊椎动物红细胞中发现的第一个珠蛋白。GBX存在于鱼的红细胞中，其亚硝酸盐还原速度比人类血红蛋白快200倍，比脑红蛋白或细胞球蛋白高50倍。脱氧银杏叶提取物在体外可将亚硝酸盐还原为一氧化氮(NO)，并能有效地抑制血小板的激活，其抑制程度比血红蛋白更大。鱼红细胞还可以将亚硝酸盐还原为NO，并比人红细胞更大程度地抑制血小板激活，而GBX基因敲除则抑制这种亚硝酸盐依赖的NO信号。对红细胞中具有主导电子转移和亚硝酸盐还原功能的新型六配位珠蛋白的描述为研究祖先血红素珠蛋白的进化信号特性提供了新的见解。
The discovery of novel globins in diverse organisms has stimulated intense interest in their evolved function, beyond oxygen binding. Globin X (GbX) is a protein found in fish, amphibians, and reptiles that diverged from a common ancestor of mammalian hemoglobins and myoglobins. Like mammalian neuroglobin, GbX was first designated as a neuronal globin in fish and exhibits six-coordinate heme geometry, suggesting a role in intracellular electron transfer reactions rather than oxygen binding. Here, we report that GbX to our knowledge is the first six-coordinate globin and the first globin protein apart from hemoglobin, found in vertebrate RBCs. GbX is present in fish erythrocytes and exhibits a nitrite reduction rate up to 200-fold faster than human hemoglobin and up to 50-fold higher than neuroglobin or cytoglobin. Deoxygenated GbX reduces nitrite to form nitric oxide (NO) and potently inhibits platelet activation in vitro, to a greater extent than hemoglobin. Fish RBCs also reduce nitrite to NO and inhibit platelet activation to a greater extent than human RBCs, whereas GbX knockdown inhibits this nitrite-dependent NO signaling. The description of a novel, six-coordinate globin in RBCs with dominant electron transfer and nitrite reduction functionality provides new insights into the evolved signaling properties of ancestral heme-globins.