Structure of TCTP reveals unexpected relationship with guanine nucleotide-free chaperones
Structure of TCTP reveals unexpected relationship with guanine nucleotide-free chaperones
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DOI：
10.1038/90415
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发表时间：
2001-08-01
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影响因子：
--
通讯作者：
Craven, CJ
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文献类型：
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作者：
Thaw, P;Baxter, NJ;Craven, CJ
肿瘤相关蛋白（TCTPs）是一类高度保守、表达丰富的真核生物蛋白家族，与细胞生长和人类急性过敏反应有关，但其细胞内生化功能尚不清楚。我们在这里报告的TCTP从裂殖酵母，其中，序列同源性的基础上，定义了整个家庭的折叠的解决方案结构。我们表明，TCTPs形成一个结构超家族与Mss 4/Dss 4家族的蛋白质，结合到GDP/GTP游离形式的Rab蛋白（Ras超家族的成员），并已被称为鸟嘌呤核苷酸自由伴侣（GFCs）。Mss 4也作为一个相对低效的鸟嘌呤核苷酸交换因子（GEF）。我们进一步表明，Mss 4上的Rab蛋白结合位点与TCTP家族中序列保守性最高的区域相一致。这是第一个链接到任何其他家族的蛋白质，已建立的TCTP家族，并建议在真核细胞中的GFC/GEF在极高的丰度的存在。
The translationally controlled tumor-associated proteins (TCTPs) are a highly conserved and abundantly expressed family of eukaryotic proteins that are implicated in both cell growth and the human acute allergic response but whose intracellular biochemical function has remained elusive. We report here the solution structure of the TCTP from Schizosaccharomyces pombe, which, on the basis of sequence homology, defines the fold of the entire family. We show that TCTPs form a structural superfamily with the Mss4/Dss4 family of proteins, which bind to the GDP/GTP free form of Rab proteins (members of the Ras superfamily) and have been termed guanine nucleotide-free chaperones (GFCs). Mss4 also acts as a relatively inefficient guanine nucleotide exchange factor (GEF). We further show that the Rab protein binding site on Mss4 coincides with the region of highest sequence conservation in the TCTP family. This is the first link to any other family of proteins that has been established for the TCTP family and suggests the presence of a GFC/GEF at extremely high abundance in eukaryotic cells.