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SUMMARY:The mechanism of retroviral DNA integration through X-ray structur
 es of its key intermediates - Peter Cherepanov\, Faculty of Medicine\, Imp
 erial College
DTSTART:20110111T161500Z
DTEND:20110111T180000Z
UID:TALK28915@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION: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 transcr
 iption\,IN catalyses two essential reactions\, 3´- end processing and str
 and 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 nu
 cleoprotein complex\, termed intasome. Upon nuclear entry\, the intasome e
 ngages host chromosomal DNA within a target capture complex to execute str
 and transfer\, irreversibly joining the viral and cellular DNA molecules. 
 We recently reported a crystal structure of the prototype foamy virus inta
 some comprising a tetramer of IN\nassembled on processed viral DNA ends (H
 are et al.\, Nature\, 2010\, 464:232-6). The structure revealed for the fi
 rst time a fully assembled IN active site\, engaged with the 3´ end of th
 e viral DNA and a pair of metal cations. We now determined crystal structu
 res of the viral nucleoprotein complex prior to 3´-processing and of the 
 intasome bound to target DNA within the pre-strand transfer and post-catal
 ytic intermediates (Maertens et al.\, Nature\, 2010\, 468: 326-329\; Hare 
 et al.\, in preparation). Collectively\, these structures illustrate all k
 ey stages of the retroviral DNA integration process\, elucidate the mechan
 ics of the IN active site and moreover provide a framework for the design 
 of INs with altered target sequences.\n
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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