EUKARYOTIC GENE REGULATION AND FUNCTION--THE METALLOTHIONEIN SYSTEM

真核基因调控与功能--金属硫蛋白系统

• 批准号: 3813334
• 负责人: D H HAMER
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3813334
• 关键词: DNA binding protein; Saccharomyces; conformation; copper; cysteine; developmental genetics; eukaryote; genetic manipulation; genetic transcription; human tissue; metallothionein; molecular cloning; nucleic acid sequence; point mutation; regulatory gene; transcription factor; transfection; zinc

Cu ions induce yeast metallothionein gene transcription by altering the conformation and DNA binding activity of the ACE1 transcription factor. We have proposed that the amino-terminal domain of ACE1 forms a polynuclear Cu(I)-S cluster, or "copper fist", which organizes the protein into a specific DNA binding factor. In support of this model, we have shown that ACE1 binds Cu(I) cooperatively, that the Cu-binding cysteine residues and DNA-binding basic residues are interdigitated within a single domain, and that a purified ACE1 peptide is luminescent. An in vitro transcription system responsive to ACE1 has been developed, and a genetic search for additional metallothionein gene transcription factors has been initiated.

铜离子通过改变酵母金属硫蛋白基因的转录水平诱导其表达 ACE 1转录因子的构象和DNA结合活性。我们 已经提出ACE 1的氨基末端结构域形成多核的 Cu（I）-S簇，或“铜拳”，将蛋白质组织成一个 特异性DNA结合因子为了支持这个模型，我们已经证明， ACE 1协同结合Cu（I），即Cu结合半胱氨酸残基和 DNA结合碱性残基在单个结构域内相互交叉，并且 纯化的ACE 1肽是发光的。体外转录 系统响应ACE 1已经开发，和遗传搜索 另外的金属硫蛋白基因转录因子已经启动。