HYDROLYSIS OF GTP BY THE ALPHA-CHAIN OF GS AND OTHER GTP BINDING-PROTEINS
HYDROLYSIS OF GTP BY THE ALPHA-CHAIN OF GS AND OTHER GTP BINDING-PROTEINS
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DOI：
10.1002/prot.340060304
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发表时间：
1989-01-01
影响因子：
2.9
通讯作者：
MASTERS, SB
中科院分区：
文献类型：
--
作者：
BOURNE, HR;LANDIS, CA;MASTERS, SB
G蛋白的功能--如细菌延伸因子(EF)Tu和21 kDa ras蛋白(P21ras)--取决于它们结合和水解GTP的能力，以及在GTP和GDP结合状态下呈现不同构象的能力。在功能和氨基酸序列上的相似性表明EF-Tu、p21ras和G蛋白α链是从原始的GTP结合蛋白进化而来的。这三个家族中的蛋白质似乎都有共同的机制，即依赖GTP的构象变化和结合的GTP的水解性。对Gs的α链的生化和分子遗传学研究指向了参与依赖α的构象变化和GTP的水解性的关键区域。α在人类脑下垂体肿瘤中的致瘤突变抑制了该蛋白的GTP酶活性，并导致腺酰环化酶活性的结构性升高。其中一个这样的突变替换了αs中对应于p21ras的Gln-61的Gln残基；这两个蛋白中该残基的突变替换抑制了它们的GTP酶活性。α中的第二类GTP酶抑制突变发生在精氨酸残基的密码子中，该残基的共价修饰也抑制了αS对GTP的水解，该精氨酸残基位于以EF-Tu或p21ras为代表的αSNOT结构域。我们认为，该结构域是GTP水解酶的内在激活剂，其功能类似于程序化核糖体对EF-Tu和新近发现的GTP酶激活蛋白对p21rass的作用。由于它们在结构和功能上的遗传相似性，我们对αS、p21ras或EF-tu作为单个分子的了解有助于我们理解超家族其他成员的重要功能。
The functions of G proteins—like those of bacterial elongation factor (EF) Tu and the 21 kDa ras proteins (p21ras)—depend upon their abilities to bind and hydrolyze GTP and to assume different conformations in GTP‐ and GDP‐bound states. Similarities in function and amino acid sequence indicate that EF‐Tu, p21ras, and G protein α‐chains evolved from a primordial GTP‐binding protein. Proteins in all three families appear to share common mechanisms for GTP‐dependent conformational change and hydrolysis of bound GTP. Biochemical and molecular genetic studies of the α‐chain of Gs(αs) point to key regions that are involved in GTP‐dependent conformational change and in hydrolysis of GTP. Tumorigenic mutations of αsin human pituitary tumors inhibit‐the protein's GTPase activity and cause constitutive elevation of adenylyl cyclase activity. One such mutation replaces a Gln residue in αsthat corresponds to Gln‐61 of p21ras; mutational replacements of this residue in both proteins inhibit their GTPase activities. A second class of the GTPase inhibiting mutations in αsoccurs in the codon for an ARG residue whose covalent modification by cholera toxin also inhibits GTP hydrolysis by αs. This Arg residue is located in a domain of αsnot represented in EF‐Tu or p21ras. We propose that this domain constitutes an intrinsic activator of GTP hydrolysis, and that it performs a function analogous to that performed for EF‐Tu by the programmed ribosome and for p21rasby the recently discovered GTPase‐activating protein. Owing to their inherited similarities of structure and function, what we learn about αs, p21ras, or EF‐tu as individual molecules helps us to understand crucial functions of other members of the super‐family.