YEAST TRANSLATION INITIATION SUPPRESSOR SUI2 ENCODES THE ALPHA-SUBUNIT OF EUKARYOTIC INITIATION FACTOR-II AND SHARES SEQUENCE IDENTITY WITH THE HUMAN ALPHA-SUBUNIT

YEAST TRANSLATION INITIATION SUPPRESSOR SUI2 ENCODES THE ALPHA-SUBUNIT OF EUKARYOTIC INITIATION FACTOR-II AND SHARES SEQUENCE IDENTITY WITH THE HUMAN ALPHA-SUBUNIT
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DOI:
10.1073/pnas.86.8.2784
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发表时间:
1989-04-01
影响因子:
11.1
通讯作者:
DONAHUE, TF
DONAHUE, TF
中科院分区:
综合性期刊1区
文献类型:
--
作者:
CIGAN, AM;PABICH, EK;DONAHUE, TF

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酵母中HIS4启动子密码子突变的遗传逆转已经确定了三个未连锁的基因,sui1、sui2和sui3(启动子密码子突变的抑制者),当突变时,尽管没有Aug起始密码子,但仍有能力在HIS4启动翻译。我们之前已经证明了SuI3基因编码β。真核生物起始因子2亚单位(eIF-2)和SuI3的锌(II)指状基序的突变改变了酵母中的起始点选择过程。在这份报告中,分子和生化特征表明Sui2抑制基因编码α。EIF-2亚基。SuI2的氨基酸序列与人eIF-2α基因编码的氨基酸序列有58%的同源性。Sui2抑制基因的突变发生在蛋白质的氨基末端部分,并改变在酵母和人类蛋白质中相同相对位置相同的氨基酸。蛋白质序列分析表明,Sui2突变酵母菌株在HIS4上没有Aug密码子的情况下,允许在UUG密码子上启动。这些数据进一步表明,eIF-2是预起始复合体的重要组成部分,它在扫描过程中介导核糖体对起始密码子的识别。
Genetic reversion of HIS4 initiator codon mutations in yeast has identified three unlinked genes, sui1, sui2, and SUI3 (suppressors of initiator codon mutations), which when mutated confer the ability to initiate translation at HIS4 despite the absence of an AUG start codon. We have previously demonstrated that the SUI3 gene encodes the .beta. subunit of the eukaryotic initiation factor 2 (eIF-2) and that mutations at a Zn(II) finger motif of SUI3 alter the start site selection process in yeast. In this report, molecular and biochemical characterizations show that the sui2 suppressor gene encodes the .alpha. subunit of eIF-2. The amino acid sequence of sui2 is 58% homologous to that encoded by the cDNA of the human eIF-2.alpha.. Mutations in the sui2 suppressor alleles occur in the amino-terminal portion of the protein and change amino acids that are identical at the same relative position in the yeast and human proteins. Protein sequence analysis shows that a sui2 mutant yeast strain allows initiation at a UUG codon in the absence of an AUG codon at HIS4. These data further suggest that eIF-2 is an important component of the preinitiation complex that mediates ribosomal recognition of a start codon during the scanning process.