Kamada Katsuhiko, Kubota Yumiko, Arata Toshiaki, Shindo Yosuke, Hanaoka Fumio
Cellular Physiology Laboratory, RIKEN Discovery Research Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Nat Struct Mol Biol. 2007 May;14(5):388-96. doi: 10.1038/nsmb1231. Epub 2007 Apr 8.
The eukaryotic GINS complex is essential for the establishment of DNA replication forks and replisome progression. We report the crystal structure of the human GINS complex. The heterotetrameric complex adopts a pseudo symmetrical layered structure comprising two heterodimers, creating four subunit-subunit interfaces. The subunit structures of the heterodimers consist of two alternating domains. The C-terminal domains of the Sld5 and Psf1 subunits are connected by linker regions to the core complex, and the C-terminal domain of Sld5 is important for core complex assembly. In contrast, the C-terminal domain of Psf1 does not contribute to the stability of the complex but is crucial for chromatin binding and replication activity. These data suggest that the core complex ensures a stable platform for the C-terminal domain of Psf1 to act as a key interaction interface for other proteins in the replication-initiation process.
真核生物GINS复合物对于DNA复制叉的建立和复制体的进展至关重要。我们报道了人类GINS复合物的晶体结构。该异源四聚体复合物采用由两个异源二聚体组成的假对称分层结构，形成四个亚基-亚基界面。异源二聚体的亚基结构由两个交替的结构域组成。Sld5和Psf1亚基的C末端结构域通过连接区域连接到核心复合物，并且Sld5的C末端结构域对于核心复合物组装很重要。相比之下，Psf1的C末端结构域对复合物的稳定性没有贡献，但对染色质结合和复制活性至关重要。这些数据表明，核心复合物确保了一个稳定的平台，使Psf1的C末端结构域能够作为复制起始过程中其他蛋白质的关键相互作用界面。
