Monomeric complex of human orphan estrogen related receptor-2 with DNA: A pseudo-dimer interface mediates extended half-site recognition
Monomeric complex of human orphan estrogen related receptor-2 with DNA: A pseudo-dimer interface mediates extended half-site recognition
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DOI：
10.1016/s0022-2836(03)00183-9
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发表时间：
2003-04-04
影响因子：
5.6
通讯作者：
Wright, PE
中科院分区：
文献类型：
--
作者：
Gearhart, MD;Holmbeck, SMA;Wright, PE
虽然大多数核受体结合DNA为同二聚体或异二聚体，但人类雌激素相关受体（hERRs）是其中的成员。孤儿受体亚家族的一种，以单体形式结合DNA。我们已经确定了hERR2与其同源DNA结合的DNA结合域（DBD）的溶液结构。核心DBD的结构和碱基相互作用与其他核受体相似。然而,。作为单体的高亲和力、序列特异性DNA结合需要在核心DBD外形成额外的碱基接触。这是通过在DBD侧翼的c端延伸（CTE）内修饰的鸟苷结合“AT-hook”来实现的，这使得碱基特异性的小凹槽相互作用。CTE的结构通过与DNA的相互作用和对通常为二聚化保留的核心DBD区域的包装来稳定。这种伪二聚体界面为扩展DNA识别提供了基础，并提出了一种机制，通过这种机制，二聚体可能是从祖先的单体受体进化而来的。2003爱思唯尔科学有限公司版权所有。
While most nuclear receptors bind DNA as homo or heterodimers, the human estrogen related receptors (hERRs) are members. of a subfamily of orphan receptors that bind DNA as monomers. We have, determined the solution structure of the DNA binding domain (DBD) of hERR2 bound to its cognate DNA. The structure and base interactions of the core DBD are similar to those of other nuclear receptors. However,. high-affinity, sequence-specific DNA binding as a monomer necessitates formation of additional base contacts outside the core DBD. This is accomplished using a modified guanosine-binding "AT-hook" within the C-terminal extension (CTE) flanking the DBD, which makes base-specific minor groove interactions. The structure of the CTE is stabilized both by interactions with the DNA and by packing against a region of the core DBD normally reserved for dimerization. This pseudo-dimer interface provides a basis for the expansion of DNA recognition and suggests a mechanism through which dimerization may have evolved from an ancestral monomeric receptor. (C) 2003 Elsevier Science Ltd. All rights reserved.