A SINGLE AMINO-ACID EXCHANGE TRANSFERS VP16-INDUCED POSITIVE CONTROL FROM THE OCT-1 TO THE OCT-2 HOMEO DOMAIN
A SINGLE AMINO-ACID EXCHANGE TRANSFERS VP16-INDUCED POSITIVE CONTROL FROM THE OCT-1 TO THE OCT-2 HOMEO DOMAIN
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DOI：
10.1101/gad.6.11.2058
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发表时间：
1992-11-01
影响因子：
10.5
通讯作者：
HERR, W
中科院分区：
文献类型：
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作者：
LAI, JS;CLEARY, MA;HERR, W
疱疹病毒反式激活因子VP 16与人Oct-1同源结构域的选择性结合是同源结构域进行差异正转录控制的模型。 VP 16通过区分Oct-1和Oct-2的7个氨基酸差异来区分密切相关的同源结构域;这些差异存在于表面上，当同源结构域与DNA结合时，这些差异被认为是可接近的。这七个差异中只有两个被VP 16识别，三-α-螺旋同源结构域的前两个α-螺旋中的每一个中有一个。与VP 16体外选择性结合和VP 16诱导的阳性对照体内选择性结合的主要决定因素是Oct-1同源结构域第一个α-螺旋中第22位的单个谷氨酸残基，但该残基的酸性性质对于与VP 16体外或体内结合并不重要，因为它可以被谷氨酰胺取代，而几乎没有或没有有害作用。仅用关键谷氨酸残基替换Oct-2同源结构域中的单个相应丙氨酸残基就足以赋予Oct-2同源结构域在体外与VP 16缔合并在体内响应VP 16诱导的阳性对照的能力。因此，同源结构域阳性对照的特异性可由单个氨基酸差异赋予。
The selective association of the herpesvirus trans-activator VP16 with the human Oct-1 homeo domain is a model for differential positive transcriptional control by homeo domains. VP16 discriminates between the closely related homeo domains of Oct-1 and Oct-2 by distinguishing among their seven amino-acid differences; these differences lie on the surface that is thought to be accessible when the homeo domain is bound to DNA. Only two of these seven differences are recognized by VP16, one in each of the first two alpha-helices of the tri-alpha-helical homeo domain. The major determinant for selective association with VP16 in vitro and VP16-induced positive control in vivo is a single glutamic acid residue at position 22 in the first alpha-helix of the Oct-1 homeo domain, but the acidic properties of this residue are not critical for association with VP16 in vitro or in vivo, because it can be replaced by glutamine with little or no deleterious effect. Mere replacement of the single corresponding alanine residue in the Oct-2 homeo domain with the key glutamic acid residue is sufficient to confer on the Oct-2 homeo domain the ability to associate with VP16 in vitro and respond to VP16-induced positive control in vivo. Thus, the specificity of homeo domain positive control can be conferred by a single amino acid difference.