3-DIMENSIONAL STRUCTURE OF AN ONCOGENE PROTEIN - CATALYTIC DOMAIN OF HUMAN C-H-RAS P21
3-DIMENSIONAL STRUCTURE OF AN ONCOGENE PROTEIN - CATALYTIC DOMAIN OF HUMAN C-H-RAS P21
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DOI：
10.1126/science.2448879
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发表时间：
1988-02-19
期刊：
影响因子：
56.9
通讯作者：
KIM, SH
中科院分区：
文献类型：
--
作者：
DEVOS, AM;TONG, L;KIM, SH
正常人c-H-ras癌基因蛋白质在2.7 nm分辨率下的晶体结构显示，该蛋白质由六股β折叠、四个α螺旋和九个连接环组成，羧基末端缺少一个柔性的18个残基。四个环参与与结合的鸟苷二磷酸的相互作用：一个与磷酸，另一个与核糖，两个与鸟嘌呤碱基。大多数转化蛋白（体内和体外）在这四个环中的三个加上一个额外的环中的几个关键位置之一具有单个氨基酸取代。其余五个环和其他暴露区域的生物功能目前尚不清楚。然而，一个环对应于中和单克隆抗体的结合位点，另一个对应于推定的“效应区”;后一个区域中的突变不改变鸟嘌呤核苷酸结合或鸟苷三磷酸酶活性，但它们确实降低了活化蛋白的转化活性。这些数据提供了一个结构基础，了解已知的生化特性正常以及activatedras癌基因蛋白质，并指出在分子中的其他区域，可能参与其他细胞功能。
The crystal structure at 2.7 Å resolution of the normal human c-H-rasoncogene protein lacking a flexible carboxyl-terminal 18 residue reveals that the protein consists of a six-stranded β sheet, four α helices, and nine connecting loops. Four loops are involved in interactions with bound guanosine diphosphate: one with the phosphates, another with the ribose, and two with the guanine base. Most of the transforming proteins (in vivo and in vitro) have single amino acid substitutions at one of a few key positions in three of these four loops plus one additional loop. The biological functions of the remaining five loops and other exposed regions are at present unknown. However, one loop corresponds to the binding site for a neutralizing monoclonal antibody and another to a putative "effector region"; mutations in the latter region do not alter guanine nucleotide binding or guanosine triphosphatase activity but they do reduce the transforming activity of activated proteins. The data provide a structural basis for understanding the known biochemical properties of normal as well as activatedrasoncogene proteins and indicate additional regions in the molecule that may possibly participate in other cellular functions.