Structural basis for octameric ring formation and DNA interaction of the human homologous-pairing protein Dmc1
Structural basis for octameric ring formation and DNA interaction of the human homologous-pairing protein Dmc1
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DOI：
10.1016/s1097-2765(04)00218-7
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发表时间：
2004-05-07
期刊：
影响因子：
16
通讯作者：
Yokoyama, S
中科院分区：
文献类型：
--
作者：
Kinebuchi, T;Kagawa, W;Yokoyama, S
人类Dmc 1蛋白是RecA/Rad 51同源物，是一种减数分裂特异性DNA重组酶，催化同源配对。RecA和Rad 51形成螺旋丝，而Dmc 1形成八聚体环。在本研究中，我们结晶的全长人Dmc 1蛋白，并解决了Dmc 1八聚体环的结构。Dmc 1蛋白的单体结构与人类和古细菌Rad 51蛋白的单体结构非常相似。除了先前在Rad 51蛋白中确定的聚合基序之外，我们在聚合物界面处发现了另一种氢键相互作用，这可以解释为什么Dmc 1形成稳定的八聚体环而不是螺旋丝。突变研究确定了内部和外部的基本补丁，是重要的同源配对。内部的补丁结合单链和双链DNA，而外部的补丁结合单链DNA。基于这些结果，我们提出了一个模型的Dmc 1环与DNA的相互作用。
The human Dmc1 protein, a RecA/Rad51 homolog, is a meiosis-specific DNA recombinase that catalyzes homologous pairing. RecA and Rad51 form helical filaments, while Dmc1 forms an octameric ring. In the present study, we crystallized the full-length human Dmc1 protein and solved the structure of the Dmc1 octameric ring. The monomeric structure of the Dmc1 protein closely resembled those of the human and archaeal Rad51 proteins. In addition to the polymerization motif that was previously identified in the Rad51 proteins, we found another hydrogen bonding interaction at the polymer interface, which could explain why Dmc1 forms stable octameric rings instead of helical filaments. Mutagenesis studies identified the inner and outer basic patches that are important for homologous pairing. The inner patch binds both single-stranded and double-stranded DNAs, while the outer one binds single-stranded DNA. Based on these results, we propose a model for the interaction of the Dmc1 rings with DNA.