Structure of the human GINS complex and its assembly and functional interface in replication initiation.
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.
Kamada
Katsuhiko
K
Cellular Physiology Laboratory, RIKEN Discovery Research Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. kamadak@riken.jp
Kubota
Yumiko
Y
Arata
Toshiaki
T
Shindo
Yosuke
Y
Hanaoka
Fumio
F
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000737:chemistry; D019281:Dimerization; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry*; D021122:Protein Subunits / Q000737:chemistry
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C521092:GINS3 protein, human; C521091:GINS4 protein, human; D046912:Multiprotein Complexes; D021122:Protein Subunits; C073119:TAP1 protein, human; C071692:TAP2 protein, human