Mechanisms of Conformational Change for a Replicative Hexameric Helicase of SV40 Large Tumor Antigen

• Published in: Cell 2004-10, Vol.119 (1), p.47-60
• Main Authors: Gai, Dahai, Zhao, Rui, Li, Dawei, Finkielstein, Carla V., Chen, Xiaojiang S.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - metabolism; Adenosine Triphosphate - metabolism; Amino Acid Sequence - genetics; Animals; Antigens, Polyomavirus Transforming - chemistry; Antigens, Polyomavirus Transforming - metabolism; Binding Sites - genetics; Crystallography, X-Ray; DNA - genetics; DNA - metabolism; DNA Helicases - chemistry; DNA Helicases - metabolism; DNA Replication - genetics; Hydrolysis; Models, Molecular; Molecular Motor Proteins - genetics; Molecular Motor Proteins - metabolism; Nucleotides - genetics; Nucleotides - metabolism; Protein Conformation; Protein Structure, Secondary - genetics; Protein Structure, Tertiary - genetics; Protein Subunits - chemistry; Protein Subunits - metabolism; Simian virus 40
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2004.09.017

The large tumor antigen (LTag) of simian virus 40, an AAA + protein, is a hexameric helicase essential for viral DNA replication in eukaryotic cells. LTag functions as an efficient molecular machine powered by ATP binding and hydrolysis for origin DNA melting and replication fork unwinding. To understand how ATP binding and hydrolysis are coupled to conformational changes, we have determined high-resolution structures (∼1.9 Å) of LTag hexamers in distinct nucleotide binding states. The structural differences of LTag in various nucleotide states detail the molecular mechanisms of conformational changes triggered by ATP binding/hydrolysis and reveal a potential mechanism of concerted nucleotide binding and hydrolysis. During these conformational changes, the angles and orientations between domains of a monomer alter, creating an “iris”-like motion in the hexamer. Additionally, six unique β hairpins on the channel surface move longitudinally along the central channel, possibly serving as a motor for pulling DNA into the LTag double hexamer for unwinding.