MULTIDOMAIN ORGANIZATION OF EUKARYOTIC GUANINE-NUCLEOTIDE EXCHANGE TRANSLATION INITIATION-FACTOR EIF-2B SUBUNITS REVEALED BY ANALYSIS OF CONSERVED SEQUENCE MOTIFS
MULTIDOMAIN ORGANIZATION OF EUKARYOTIC GUANINE-NUCLEOTIDE EXCHANGE TRANSLATION INITIATION-FACTOR EIF-2B SUBUNITS REVEALED BY ANALYSIS OF CONSERVED SEQUENCE MOTIFS
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DOI：
10.1002/pro.5560040819
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发表时间：
1995-08-01
期刊：
影响因子：
8
通讯作者：
KOONIN, EV
中科院分区：
文献类型：
--
作者：
KOONIN, EV
计算机辅助分析的氨基酸序列使用的方法进行数据库筛选与个别序列和多个比对块揭示了一个复杂的多域组织的酵母蛋白GCD 6和GCD 1，和哺乳动物同源物的GCD 6亚基的真核翻译起始因子eIF-2B参与GDP/GTP交换eIF-2。结果表明，这些蛋白质含有一个假定的核苷酸结合结构域相关的各种核苷酸转移酶，其中大多数是参与核苷二磷酸糖的形成在细菌中。三个保守的基序，其中之一似乎是一个变体的磷酸盐结合位点（P-环）和另一个可能被认为是一个特定的版本的Mg 2+结合位点的NTP利用酶，被确定在核苷酸转移酶相关的结构域。与邻近P环的第三个独特基序一起，这些基序包含核苷酸结合结构域的新超家族的特征。由六肽氨基酸重复序列组成的结构域，具有周期性分布的大体积疏水残基（异亮氨酸补丁），这在以前已经在细菌乙酰转移酶中被确定，位于核苷酸转移酶相关结构域的C-末端。最后，在GCD 6、eIF-2B β和其他两个真核翻译起始因子eIF-4 γ和eIF-5的C末端，存在一个以前未检测到的保守结构域。假设核苷酸转移酶相关结构域直接参与GDP/GTP交换，而C-末端保守结构域可能参与eIF-2B、eIF-4 γ和eIF-5与eIF-2的相互作用。
Computer-assisted analysis of amino acid sequences using methods for database screening with individual sequences and with multiple alignment blocks reveals a complex multidomain organization of yeast proteins GCD6 and GCD1, and mammalian homolog of GCD6-subunits of the eukaryotic translation initiation factor eIF-2B involved in GDP/GTP exchange on eIF-2. It is shown that these proteins contain a putative nucleotide-binding domain related to a variety of nucleotidyltransferases, most of which are involved in nucleoside diphosphate-sugar formation in bacteria. Three conserved motifs, one of which appears to be a variant of the phosphate-binding site (P-loop) and another that may be considered a specific version of the Mg2+-binding site of NTP-utilizing enzymes, were identified in the nucleotidyltransferase-related domain. Together with the third unique motif adjacent to the P-loop, these motifs comprise the signature of a new superfamily of nucleotide-binding domains. A domain consisting of hexapeptide amino acid repeats with a periodic distribution of bulky hydrophobic residues (isoleucine patch), which previously have been identified in bacterial acetyltransferases, is located toward the C-terminus from the nucleotidyltransferase-related domain. Finally, at the very C-termini of GCD6, eIF-2B epsilon, and two other eukaryotic translation initiation factors, eIF-4 gamma and eIF-5, there is a previously undetected, conserved domain. It is hypothesized that the nucleotidyltransferase-related domain is directly involved in the GDP/GTP exchange, whereas the C-terminal conserved domain may be involved in the interaction of eIF-2B, eIF-4 gamma, and eIF-5 with eIF-2.