title: The structure of SV40 large T hexameric helicase in complex with AT-rich origin DNA.
abstract: DNA replication is a fundamental biological process. The initial step in eukaryotic DNA replication is the assembly of the pre-initiation complex, including the formation of two head-to-head hexameric helicases around the replication origin. How these hexameric helicases interact with their origin dsDNA remains unknown. Here, we report the co-crystal structure of the SV40 Large-T Antigen (LT) hexameric helicase bound to its origin dsDNA. The structure shows that the six subunits form a near-planar ring that interacts with the origin, so that each subunit makes unique contacts with the DNA. The origin dsDNA inside the narrower AAA+ domain channel shows partial melting due to the compression of the two phosphate backbones, forcing Watson-Crick base-pairs within the duplex to flip outward. This structure provides the first snapshot of a hexameric helicase binding to origin dsDNA, and suggests a possible mechanism of origin melting by LT during SV40 replication in eukaryotic cells.
authors.affiliation: Departments of Biological Sciences and Chemistry, Molecular and Computational Biology Program, University of Southern California, Los Angeles, United States.
authors.forename: Dahai
authors.initials: D
authors.lastname: Gai
authors.affiliation: Department of Biological Sciences, Genetic, Molecular and Cellular Biology Program, Keck School of Medicine, University of Southern California, Los Angeles, United States.
authors.forename: Damian
authors.initials: D
authors.lastname: Wang
authors.affiliation: Center of Excellence in NanoBiophysics, University of Southern California, Los Angeles, United States.
authors.forename: Shu-Xing
authors.initials: SX
authors.lastname: Li
authors.affiliation: Departments of Biological Sciences and Chemistry, Molecular and Computational Biology Program, University of Southern California, Los Angeles, United States.|Department of Biological Sciences, Genetic, Molecular and Cellular Biology Program, Keck School of Medicine, University of Southern California, Los Angeles, United States.|Center of Excellence in NanoBiophysics, University of Southern California, Los Angeles, United States.|Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, United States.
authors.forename: Xiaojiang S
authors.identifier: 0000-0001-9574-0551
authors.initials: XS
authors.lastname: Chen
mesh_terms: D000952:Antigens, Polyomavirus Transforming / Q000737:chemistry* / Q000378:metabolism*; D000957:Antigens, Viral, Tumor / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D018741:Replication Origin; D013539:Simian virus 40 / Q000201:enzymology*
chemical_list: D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor; D004247:DNA
keywords: APOBEC deaminase; DNA replication; E. coli; biophysics; human; structural biology; virus