COOPERATIVE DIMERIZATION OF PAIRED CLASS HOMEO DOMAINS ON DNA
COOPERATIVE DIMERIZATION OF PAIRED CLASS HOMEO DOMAINS ON DNA
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DOI：
10.1101/gad.7.11.2120
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发表时间：
1993-11-01
影响因子：
10.5
通讯作者：
DESPLAN, C
中科院分区：
文献类型：
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作者：
WILSON, D;SHENG, GJ;DESPLAN, C
真核生物中含有同源结构域的蛋白质介导许多转录过程。因为几乎所有的动物同源蛋白都被认为与短的、高度相关的DNA序列结合，所以它们高度特异性作用的基础还不清楚。我们表明，回文DNA序列上的合作二聚化可以提供增加的特异性的三个主要类别的同源结构域之一，配对/Pax类。来自这类的60个氨基酸的同源结构域包含足够的信息以作为同源二聚体和异源二聚体与回文DNA序列协同结合;也就是说，一个同源结构域分子的结合可以使第二个分子的亲和力增加高达300倍。同源结构域的配对（Prd）类的不同成员偏好半位点之间的不同间距，如由识别螺旋的第九个氨基酸残基所确定的。此外，该残基决定了回文位点中心碱基对的身份，以及协同相互作用的大小。在Prd类中同源结构域的合作二聚化将它们与其他类区分开来，而结合位点的构型和序列特异性允许在该类内进行区分。
Homeo domain-containing proteins mediate many transcriptional processes in eukaryotes. Because nearly all animal homeo proteins are believed to bind to short, highly related DNA sequences, the basis for their high specificity of action is not understood. We show that cooperative dimerization on palindromic DNA sequences can provide increased specificity to one of the three major classes of homeo domains, the Paired/Pax class. The 60-amino-acid homeo domains from this class contain sufficient information to bind cooperatively as homo- and heterodimers to palindromic DNA sequences; that is, the binding of one homeo domain molecule can increase the affinity of a second molecule by up to 300-fold. Different members of the Paired (Prd) class of homeo domains prefer different spacings between half-sites, as determined by the ninth amino acid residue of the recognition helix. In addition, this residue determines the identity of the base pairs at the center of the palindromic sites, as well as the magnitude of the cooperative interaction. The cooperative dimerization of homeo domains in the Prd class distinguishes them from other classes, whereas binding-site configuration and sequence specificity allow for distinctions within this class.