INTERACTIONS BETWEEN HETEROLOGOUS HELIX-LOOP-HELIX PROTEINS GENERATE COMPLEXES THAT BIND SPECIFICALLY TO A COMMON DNA-SEQUENCE
INTERACTIONS BETWEEN HETEROLOGOUS HELIX-LOOP-HELIX PROTEINS GENERATE COMPLEXES THAT BIND SPECIFICALLY TO A COMMON DNA-SEQUENCE
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DOI：
10.1016/0092-8674(89)90434-0
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发表时间：
1989-08-11
期刊：
影响因子：
64.5
通讯作者：
BALTIMORE, D
中科院分区：
文献类型：
--
作者：
MURRE, C;MCCAW, PS;BALTIMORE, D
最近在多种蛋白质中发现了具有明显两亲性螺旋（HLH 基序）的 DNA 结合和二聚化基序，其中包括两种与免疫球蛋白增强子（E12 和 E47）结合的蛋白。我们在此表明，各种 HLH 蛋白可以作为表观异二聚体结合到单个 DNA 基序上，也可以作为表观同二聚体（尽管通常较弱）结合。 HLH 结构域可以介导无子体、E12 或 E47（A 类）与 achaete-scute T3 或 MyoD（B 类）之间的异二聚体形成，以形成对免疫球蛋白 kappa 链增强子中的 .kappa.E2 位点具有高亲和力的蛋白质。 Achaete-scute T3 和 MyoD 蛋白不一起形成 κE2 结合异二聚体，并且没有明显的与 N-myc 的活性复合物。无子体T3产物和无子体T3产物之间异二聚体的形成可以解释这两个位点突变体的相似表型以及它们之间的遗传相互作用。 E12 和 E47 在哺乳动物发育中的作用很可能类似于果蝇中无女儿的作用。
A DNA binding and dimerization motif, with apparent amphipathic helices (the HLH motif), has recently been identified in various proteins, including two that bind to immunoglobulin enhancers (E12 and E47). We show here that various HLH proteins can bind as apparent heterodimers to a single DNA motif and also, albeit usually more weakly, as apparent homodimers. The HLH domain can mediate heterodimer formation between either daughterless, E12, or E47 (Class A) and achaete-scute T3 or MyoD (Class B) to form proteins with high affinity for the .kappa.E2 site in the immunoglobulin kappa chain enhancer. The achaete-scute T3 and MyoD proteins do not form .kappa.E2-binding heterodimers together, and no active complex with N-myc was evident. The formation of a heterodimer between the daughterless and achaete-scute T3 products may explain the similar phenotypes of mutants at these two loci and the genetic interactions between them. A role of E12 and E47 in mammalian development, analogous to that of daughterless in Drosophila, is likely.