CRYSTAL-STRUCTURE OF THE MATA1/MAT-ALPHA-2 HOMEODOMAIN HETERODIMER BOUND TO DNA
CRYSTAL-STRUCTURE OF THE MATA1/MAT-ALPHA-2 HOMEODOMAIN HETERODIMER BOUND TO DNA
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DOI：
10.1126/science.270.5234.262
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发表时间：
1995-10-13
期刊：
影响因子：
56.9
通讯作者：
WOLBERGER, C
中科院分区：
文献类型：
--
作者：
LI, T;STARK, MR;WOLBERGER, C
酿酒酵母MATa 1和MAT α 2同源结构域蛋白在决定酵母细胞类型中发挥作用，形成异二聚体，其结合DNA并以细胞类型特异性方式抑制转录。尽管α 2和α 1蛋白本身对DNA仅具有适度的亲和力，但α 1/α 2异二聚体以高特异性和亲和力结合DNA。以2.5埃的分辨率测定与DNA结合的α 1/α 2同源结构域异源二聚体的三维晶体结构。α 1和α 2同源结构域以头-尾方向结合，异二聚体接触由位于α 2同源结构域羧基末端的16个残基的尾部介导。这条尾巴在a1的存在下变得有序，它的一部分形成了一个短的两亲性螺旋，该螺旋与螺旋1和2之间的a1同源结构域相对应。在DNA中诱导明显的60度弯曲，这使得可能的蛋白质-蛋白质和蛋白质-DNA接触，而这在直的DNA片段中不能发生。由连接到稳定折叠的DNA结合结构域的柔性蛋白质识别肽介导的复合物形成可能被证明是其他类真核转录调控因子的结构的一般特征。
The Saccharomyces cerevisiae MATa1 and MAT alpha 2 homeodomain proteins, which play a role in determining yeast cell type, form a heterodimer that binds DNA and represses transcription in a cell type-specific manner. Whereas the alpha 2 and a1 proteins on their own have only modest affinity for DNA, the a1/alpha 2 heterodimer binds DNA with high specificity and affinity. The three-dimensional crystal structure of the a1/alpha 2 homeodomain heterodimer bound to DNA was determined at a resolution of 2.5 Angstrom. The a1 and alpha 2 homeodomains bind in a head-to-tail orientation, with heterodimer contacts mediated by a 16-residue tail located carboxyl-terminal to the alpha 2 homeodomain. This tail becomes ordered in the presence of a1, part of it forming a short amphipathic helix that packs against the a1 homeodomain between helices 1 and 2. A pronounced 60 degrees bend is induced in the DNA, which makes possible protein-protein and protein-DNA contacts that could not take place in a straight DNA fragment. Complex formation mediated by flexible protein-recognition peptides attached to stably folded DNA binding domains may prove to be a general feature of the architecture of other classes of eukaryotic transcriptional regulators.