Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins
Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins
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DOI：
10.1038/35000617
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发表时间：
2000-02-03
期刊：
影响因子：
64.8
通讯作者：
Herrmann, C
中科院分区：
文献类型：
--
作者：
Prakash, B;Praefcke, GJK;Herrmann, C
干扰素-γ是一种免疫调节物质，其诱导许多基因的表达以协调细胞应答并建立细胞的抗病毒状态。γ-干扰素诱导的最丰富的抗病毒蛋白是鸟苷酸结合蛋白，如GBP 1和GBP 2（参考文献1，2）。这些是相对分子质量为67，000的大GTP结合蛋白，具有高转换GTP酶活性（3）和抗病毒作用（4）。在这里，我们已经确定了全长人GBP 1的晶体结构，分辨率为1.8埃。氨基端的278个残基构成了一个修饰的G结构域，与典型的PAS结构相比，有许多插入，羧基端部分是一个具有独特功能的扩展螺旋结构域。根据本文报道的结构和生化实验，GBP 1似乎属于包括Mx和发动蛋白的大GTP结合蛋白组，其共同特性是能够以高浓度依赖性GTP酶活性进行寡聚化（5）。
Interferon-gamma is an immunomodulatory substance that induces the expression of many genes to orchestrate a cellular response and establish the antiviral state of the cell. Among the most abundant antiviral proteins induced by interferon-gamma are guanylate-binding proteins such as GBP1 and GBP2 (refs 1, 2). These are large GTP-binding proteins of relative molecular mass 67,000 with a high-turnover GTPase activity(3) and an antiviral effect(4). Here we have determined the crystal structure of full-length human GBP1 to 1.8 Angstrom resolution. The amino-terminal 278 residues constitute a modified G domain with a number of insertions compared to the canonical pas structure, and the carboxy-terminal part is an extended helical domain with unique features. From the structure and biochemical experiments reported here, GBP1 appears to belong to the group of large GTP-binding proteins that includes Mx and dynamin, the common property of which is the ability to undergo oligomerization with a high concentration-dependent GTPase activity(5).