Analysis of the costructure of the simian virus 40 T-antigen origin binding domain with site I reveals a correlation between GAGGC spacing and spiral assembly.
Analysis of the costructure of the simian virus 40 T-antigen origin binding domain with site I reveals a correlation between GAGGC spacing and spiral assembly.
复制标题
对猿猴病毒 40 T 抗原起源结合域与位点 I 的结构分析揭示了 GAGGC 间距与螺旋组装之间的相关性。
DOI：
10.1128/jvi.02549-12
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发表时间：
2013
影响因子：
5.4
通讯作者：
Bullock,PeterA
中科院分区：
文献类型：
--
作者：
Meinke,Gretchen;Phelan,PaulJ;Harrison,CeliaJ;Bullock,PeterA
多瘤病毒的复制起点包括多次出现G(A/G)GGC，这是病毒启动子T抗原(T-Ag)的高亲和力结合元件。猴病毒40的I位调控区参与转录抑制和DNA复制启动，含有两个GAGGC序列，由7个碱基的富含AT的序列隔开。我们已经解决了与第I位结合的SV40起始结合结构域(OBD)的3.2°共结构。我们还证实了T-ag在第I位的组装仅限于形成单一的六聚体。这些观察结果使得分析与I位五核苷酸结合的脱氧核糖核酸在六聚体形成中的作用成为可能(S)。有趣的是，他们揭示了与I位点结合的OBD与先前描述的六面螺旋结构中的一对OBD亚基之间的相关性。基于这些发现，我们认为螺旋组装是由头到尾排列的五核苷酸对促进的。最后，讨论了OBD亚基螺旋组装的可能性，解释了在多瘤病毒复制起源中发现的五核苷酸的异质性分布。
Polyomavirus origins of replication contain multiple occurrences of G(A/G)GGC, the high-affinity binding element for the viral initiator T-antigen (T-ag). The site I regulatory region of simian virus 40, involved in the repression of transcription and the enhancement of DNA replication initiation, contains two GAGGC sequences arranged head to tail and separated by a 7-bp AT-rich sequence. We have solved a 3.2-Å costructure of the SV40 origin-binding domain (OBD) bound to site I. We have also established that T-ag assembly on site I is limited to the formation of a single hexamer. These observations have enabled an analysis of the role(s) of the OBDs bound to the site I pentanucleotides in hexamer formation. Of interest, they reveal a correlation between the OBDs bound to site I and a pair of OBD subunits in the previously described hexameric spiral structure. Based on these findings, we propose that spiral assembly is promoted by pentanucleotide pairs arranged in a head-to-tail manner. Finally, the possibility that spiral assembly by OBD subunits accounts for the heterogeneous distribution of pentanucleotides found in the origins of replication of polyomaviruses is discussed.