A novel DNA recognition mode by the NF-κB p65 homodimer
A novel DNA recognition mode by the NF-κB p65 homodimer
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DOI：
10.1038/nsb0198-67
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发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Ghosh, G
中科院分区：
文献类型：
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作者：
Chen, YQ;Ghosh, S;Ghosh, G
与DNA靶复合的NF-κ B p65（ReIA）同二聚体的晶体结构已被确定为2.4埃分辨率。两个p65亚基不对称地布置在DNA靶上，同二聚体应最佳地结合至假回文九碱基对靶，其中每个亚基识别由中心A-T碱基对隔开的5 '-GAAA-3'半位点，然而，亚基之一（亚基B）遇到5 '-GAAA-3'的半位点。从G-C到A-T的单个碱基对变化导致该半位点与亚基B中的碱基接触蛋白残基之间的高度不利的相互作用，这导致N-末端末端结构域从其正常构象旋转18度。值得注意的是，亚基B保留了与DNA靶标的糖磷酸骨架的所有相互作用。这种相互作用模式允许NF-κ B p65同二聚体识别仅含有一个同源半位点的DNA靶。另一半位点序列的差异提供了复合物构象和亲和力的变化。
The crystal structure of the NF-kappa B p65 (ReIA) homodimer in complex with a DNA target has been determined to 2.4 Angstrom resolution. The two p65 subunits are not symmetrically disposed on the DNA target, The homodimer should optimally bind to a pseudo-palindromic nine base pair target with each subunit recognizing a 5'GGAA-3' half site separated by a central A-T base pair, However, one of the subunits (subunit B) encounters a half site of 5'-GAAA-3'. The single base-pair change from G-C to A-T results in highly unfavorable interactions between this half site and the base contacting protein residues in subunit B, which leads to an 18 degrees rotation of the N-terminal terminal domain from its normal conformation. Remarkably, subunit B retains all the interactions with the sugar phosphate backbone of the DNA target. This mode of interaction allows the NF-kappa B p65 homodimer to recognize DNA targets containing only one cognate half site. Differences in the sequence of the other half site provide variations in conformation and affinity of the complex.