title: Structure of the human GINS complex and its assembly and functional interface in replication initiation.
abstract: 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.
authors.affiliation: Cellular Physiology Laboratory, RIKEN Discovery Research Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. kamadak@riken.jp
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kamada
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kubota
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Arata
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shindo
authors.forename: Fumio
authors.initials: F
authors.lastname: Hanaoka
mesh_terms: 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
chemical_list: 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