Structure of Cre recombinase complexed with DNA in a site-specific recombination synapse
Structure of Cre recombinase complexed with DNA in a site-specific recombination synapse
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DOI：
10.1038/37925
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发表时间：
1997-09-04
期刊：
影响因子：
64.8
通讯作者：
VanDuyne, GD
中科院分区：
文献类型：
--
作者：
Guo, F;Gopaul, DN;VanDuyne, GD
在定点DNA重组过程中，重组酶识别特定的DNA序列，催化这些位点之间的DNA链的相互交换，从而在病毒整合、切除和染色体分离等过程中实现基因重排。噬菌体重组酶Cre催化两个34碱基对的loxP位点之间的定点重组。结合在AloxP底物上的Cre在2.4埃分辨率下的晶体结构揭示了重组反应中的中间体，即Cre分子裂解底物与DNA形成共价的3‘-磷酸酪氨酸键。四个重组酶和两个loxP位点形成了一个突触结构，其中的DNA类似于四向Holliday连接中间体的模型。Cre-loxP复合体挑战了需要在四元结构中进行较大变化的特定位点重组模型。相反，Cre亚基的羧基末端的细微变构变化可能会协调切割和链交换反应。
During site-specific DMA recombination, which brings about genetic rearrangement in processes such as viral integration and excision and chromosomal segregation, recombinase enzymes recognize specific DNA sequences and catalyse the reciprocal exchange of DNA strands between these sites. The bacteriophage recombinase Cre catalyses site-specific recombination between two 34-base-pair loxP sites. The crystal structure at 2.4 Angstrom resolution of Cre bound to aloxP substrate reveals an intermediate in the recombination reaction, fin which a Cre molecule has cleaved the substrate to form a covalent 3'-phosphotyrosine linkage with the DNA. Four recombinases and two loxP sites form a synapsed structure in which the DNA resembles models of four-way Holliday-junction intermediates. The Cre-loxP complex challenges models of site-specific recombination that require large changes in quaternary structure. Subtle allosteric changes at the carboxy termini of the Cre subunits may instead coordinate the cleavage and strand-exchange reactions.