Retrovirus Integrase-DNA Structure Elucidates Concerted Integration Mechanisms 英文参考文献.docVIP

Viruses 2010, 2, 1185-1189; doi:10.3390/v2051185 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Commentary Retrovirus Integrase-DNA Structure Elucidates Concerted Integration Mechanisms Duane Grandgenett 1,* and Sergey Korolev 2 1 Saint Louis University School of Medicine, Institute for Molecular Virology, 1100 S. Grand Blvd., St. Louis, MO 63104, USA 2 Department of Biochemistry and Molecular Biology, 1100 S. Grand Blvd., St. Louis, MO 63104, USA; E-Mail: korolevs@ * Author to whom correspondence should be addressed; E-Mail: grandgdp@; Tel.: +1 314-977-8784; Fax: +1 314-977-8798. Received: 19 April 2010; in revised form: 7 May 2010 / Accepted: 7 May 2010 / Published: 10 May 2010 Abstract: Commentary on Hare, S.; Gupta, S.S.; Valkov, E.; Engelman, A.; Cherepanov, P. Retroviral intasome assembly and inhibition of DNA strand transfer. Nature 2010, 464, 232-236. In the 11 March 2010 issue of Nature, Peter Cherepanov and colleagues from the Imperial College, London, determined the crystal structure of the prototype foamy virus (PFV) integrase (IN) in complex with its viral DNA [1]. IN has multiple roles in the retrovirus life cycle. In virus-infected cells, IN is located in the cytoplasmic preintegration complex (PIC) where it cleaves a dinucleotide from the 3’ OH DNA blunt-ends. Upon nuclear transport, IN promotes the concerted integration of the recessed linear DNA ends into opposite strands of the selected host site. The insertion of the viral DNA into the host genome results in a small duplication of cellular DNA sequences. The Nature paper by Cherepanov and colleagues has provided the first atomic resolution view of a DNA-bound structure of four PFV IN monomers (Figure 1). The complex is termed intasome [2]. The crystal structure captures a functional intasome possessing two 3’ OH recessed DNA ends which is capable of concerted integration. In this structure, the non-tran