TRANSITION-METALS IN CONTROL OF GENE-EXPRESSION
TRANSITION-METALS IN CONTROL OF GENE-EXPRESSION
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DOI：
10.1126/science.8342038
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发表时间：
1993-08-06
期刊：
影响因子：
56.9
通讯作者：
OHALLORAN, TV
中科院分区：
文献类型：
--
作者：
OHALLORAN, TV
金属蛋白在基因表达中起结构和催化作用。金属调节蛋白是一个亚类，其对参与呼吸、代谢和金属特异性稳态或应激反应系统（如铁吸收和储存、铜流出和汞解毒）的基因施加金属响应控制。在金属调节系统中首次发现了两种控制基因表达的变构机制：铁蛋白产生的铁响应性翻译控制机制和解毒基因转录控制的汞响应性DNA畸变机制。当金属离子浓度超过危险阈值时，这些原本不相关的机制引起快速的生理反应。这些变构金属离子受体的分子识别是通过非典型的配位几何结构、簇形成或与辅基（如硫化物和血红素）的络合物来实现的。因此，许多无机组件，否则支持的结构的生物聚合物或催化底物转化的酶的活性位点也已适应担任传感器功能的金属调节蛋白。这些金属传感器蛋白质相互作用的机制研究提供了新的见解无机化学，分子生物学和细胞生理学的基本方面。
Metalloproteins play structural and catalytic roles in gene expression. The metalloregulatory proteins are a subclass that exerts metal-responsive control of genes involved in respiration, metabolism, and metal-specific homeostasis or stress-response systems, such as iron uptake and storage, copper efflux, and mercury detoxification. Two allosteric mechanisms for control of gene expression were first discovered in metalloregulatory systems: an iron-responsive translational control mechanism for ferritin production and a mercury-responsive DNA-distortion mechanism for transcriptional control of detoxification genes. These otherwise unrelated mechanisms give rise to a rapid physiological response when metal ion concentrations exceed a dangerous threshold. Molecular recognition in these allosteric metal ion receptors is achieved through atypical coordination geometries, cluster formation, or complexes with prosthetic groups, such as sulfide and heme. Thus, many of the inorganic assemblies that otherwise buttress the structure of biopolymers or catalyze substrate transformation in active sites of enzymes have also been adapted to serve sensor functions in the metalloregulatory proteins. Mechanistic studies of these metal-sensor protein interactions are providing new insights into fundamental aspects of inorganic chemistry, molecular biology, and cellular physiology.