The mechanism of retroviral DNA integration through X-ray structures of its key intermediates
Event details
| Date | 02.02.2011 |
| Hour | 17:00 |
| Speaker | Peter Cherepanov, PhD |
| Location |
SV 1717 A
|
| Category | Conferences - Seminars |
To establish successful infection, a retrovirus must insert a DNA replica of its genome into host cell chromosomal DNA. This process is orchestrated by integrase (IN), a viral enzyme that belongs to the DDE(D) nucleotidyltransferase/transposase superfamily. Following reverse transcription, IN catalyses two essential reactions, 3´-end processing and strand transfer, acting upon both ends of the linear viral DNA. To carry out these functions IN synapses the viral DNA ends forming a highly stable nucleoprotein complex, termed intasome. Upon nuclear entry, the intasome engages host chromosomal DNA within a target capture complex to execute strand transfer, irreversibly joining the viral and cellular DNA molecules.
We reported a crystal structure of the prototype foamy virus intasome comprising a tetramer of IN assembled on processed viral DNA ends (Hare et al., Nature, 2010, 464:232-6). The structure revealed for the first time a fully assembled IN active site, engaged with the 3´ end of the viral DNA and a pair of metal cations. More recently determined crystal structures of the viral nucleoprotein complex prior to 3´-processing (in preparation for publication) and of the intasome bound to target DNA within the pre-strand transfer and post-catalytic intermediates (Maertens et al., Nature, 2010, 468:326-329). Collectively, these structures illustrate all key stages of the retroviral DNA integration process, elucidate the mechanics of the IN active site and moreover provide a framework for the design of INs with altered target sequences.
Practical information
- General public
- Free
Contact
- Didier Trono