SV40 large T antigen hexamer structure: domain organization and DNA-induced conformational changes

Current Biology : CB
Margaret S VanLoockE H Egelman

Abstract

Simian Virus 40 replication requires only one viral protein, the Large T antigen (T-ag), which acts as both an initiator of replication and as a replicative helicase (reviewed in ). We used electron microscopy to generate a three-dimensional reconstruction of the T-ag hexameric ring in the presence and absence of a synthetic replication fork to locate the T-ag domains, to examine structural changes in the T-ag hexamer associated with DNA binding, and to analyze the formation of double hexamers on and off DNA. We found that binding DNA to the T-ag hexamer induces large conformational changes in the N- and C-terminal domains of T-ag. Additionally, we observed a significant increase in density throughout the central channel of the hexameric ring upon DNA binding. We conclude that conformational changes in the T-ag hexamer are required to accommodate DNA and that the mode of DNA binding may be similar to that suggested for some other ring helicases. We also identified two conformations of T-ag double hexamers formed in the presence of forked DNA: with N-terminal hexamer-hexamer contacts, similar to those formed on origin DNA, or with C-terminal contacts, which are unlike any T-ag double hexamers reported previously.

References

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Citations

Apr 6, 2005·Journal of Molecular Biology·Sjors H W ScheresJose-Maria Carazo
Mar 24, 2004·Journal of Structural Biology·Lakshminarayan M IyerL Aravind
Sep 11, 2002·Journal of Molecular Biology·Shixin YangEdward H Egelman
Sep 25, 2003·Nature Reviews. Molecular Cell Biology·Arne Stenlund
May 21, 2011·Nucleic Acids Research·Brent E SteadMegan J Davey
Feb 16, 2007·Journal of Virology·Weiping WangDaniel T Simmons
Apr 14, 2006·Journal of Virology·Gretchen MeinkeAndrew Bohm
May 13, 2006·Annual Review of Biophysics and Biomolecular Structure·Kakoli Mitra, Joachim Frank
Mar 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Mona T NorcumStephen J Benkovic
Aug 12, 2004·Molecular Cell·Daniel L Kaplan, Mike O'Donnell
Aug 9, 2003·Structure·J Anson JamesAneel K Aggarwal
Feb 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Seung-Jae LeeLeemor Joshua-Tor
Feb 17, 2006·Journal of Molecular Biology·Mikel ValleJosé María Carazo
Jan 1, 2012·Genes·Daniel T Simmons
Jul 14, 2017·Journal of Virology·Julianna S DeakynePaul M Lieberman
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Sep 19, 2003·The Journal of Biological Chemistry·Daniel L KaplanMike O'Donnell
Jun 10, 2009·Journal of Cellular Biochemistry·Daniela M RothDavid A Jans

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