The structure of SV40 large T hexameric helicase in complex with AT-rich origin DNA

• Main Authors: Dahai Gai, Damian Wang, Shu-Xing Li, Xiaojiang S Chen
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2016-12-01
• Series: eLife
• Subjects: structural biology; DNA replication; APOBEC deaminase
• Online Access: https://elifesciences.org/articles/18129

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.