RETRACTED: The structure of SV40 large T hexameric helicase in complex with AT-rich origin DNA
Dahai Gai,
Damian Wang,
Shu-Xing Li,
Xiaojiang S Chen
Affiliations
Dahai Gai
Departments of Biological Sciences and Chemistry, Molecular and Computational Biology Program, University of Southern California, Los Angeles, United States
Damian Wang
Department of Biological Sciences, Genetic, Molecular and Cellular Biology Program, Keck School of Medicine, University of Southern California, Los Angeles, United States
Shu-Xing Li
Center of Excellence in NanoBiophysics, University of Southern California, Los Angeles, United States
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
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.
