Sandbox Reserved 958: Difference between revisions
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- ''in vivo'' it catalyzes the '''transport the viral DNA into the nucleus''', it interacts with many proteins ('''VPR, VBP1, HIV-matrix,...''') and DNA to form the '''Pre-Integration Complex''' ('''PIC''') and allow the integration of the viral DNA into host genome and this mechanism can be divided in two reactions, the '''3'-Processing''' and the '''Strand Transfer'''<ref name="Dells">PMID: 19091057</ref> | - ''in vivo'' it catalyzes the '''transport the viral DNA into the nucleus''', it interacts with many proteins ('''VPR, VBP1, HIV-matrix,...''') and DNA to form the '''Pre-Integration Complex''' ('''PIC''') and allow the integration of the viral DNA into host genome and this mechanism can be divided in two reactions, the '''3'-Processing''' and the '''Strand Transfer'''<ref name="Dells">PMID: 19091057</ref> | ||
[[Image:3108751 idr-4-065f1.png]] | |||
- ''in vitro'' researchers proved that two more reactions can be catalyzed by the integrase, the '''disintegration''' of the viral DNA and also a possible '''DNA polymerase activity'''<ref name="Liao">PMID:21426159</ref> to repair mismatches during integration. | - ''in vitro'' researchers proved that two more reactions can be catalyzed by the integrase, the '''disintegration''' of the viral DNA and also a possible '''DNA polymerase activity'''<ref name="Liao">PMID:21426159</ref> to repair mismatches during integration. | ||
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The strand transfer is the really integration step, it provokes the integration of the viral DNA into the host genome by two sequential transesterifications. The integration site is a palindromic and symmetric sequence composed of five nucleotides. This sequence is cleaved to allow the fusion of the LTR extremities of the viral DNA. Afterwards two 3' nucleotides are excised and the joining strand of the five nucleotides is full-filed<ref name="Mbisa">PMID:21694910</ref>. The structure that permits this transfer is the intasome (viral DNA + integrase) by association with the '''Lens Epithelium-derived Growth factor (LEDGF)''' and the '''p75''' protein that has a cofactor activity for integrase and is a tethering site for chromatin binding. | The strand transfer is the really integration step, it provokes the integration of the viral DNA into the host genome by two sequential transesterifications. The integration site is a palindromic and symmetric sequence composed of five nucleotides. This sequence is cleaved to allow the fusion of the LTR extremities of the viral DNA. Afterwards two 3' nucleotides are excised and the joining strand of the five nucleotides is full-filed<ref name="Mbisa">PMID:21694910</ref>. The structure that permits this transfer is the intasome (viral DNA + integrase) by association with the '''Lens Epithelium-derived Growth factor (LEDGF)''' and the '''p75''' protein that has a cofactor activity for integrase and is a tethering site for chromatin binding. | ||
== Posttranslationnal Modifications == | == Posttranslationnal Modifications == | ||
Studies have prooved that 4 different kind of Post Translationnal Modifications (PTMs) affect the HIV-1 integrase : ubiquitination, SUMOylation, acetylation and phosphorylation. Furthermore there are proteins that counteract or facilitate these PTMs implantation. On one hand p300 and GCN5 can acetylate IN mostly on its C-ter domain while in the other hand Ku70 reduces the ubiquitination level of the N-ter domain (K6, K11, K27, K29, K33, K48 and K63). Another study also found that IN contains three ψ-K-x-D/E motifs, which can be SUMOylated at three Lys residues, K46,<scene name='60/604477/Sumoylation/1'>K136</scene> and K244 <ref name="Terreni">PMID:20226045</ref>. | Studies have prooved that 4 different kind of Post Translationnal Modifications (PTMs) affect the HIV-1 integrase : ubiquitination, SUMOylation, acetylation and phosphorylation. Furthermore there are proteins that counteract or facilitate these PTMs implantation. On one hand p300 and GCN5 can acetylate IN mostly on its C-ter domain while in the other hand Ku70 reduces the ubiquitination level of the N-ter domain (K6, K11, K27, K29, K33, K48 and K63). Another study also found that IN contains three ψ-K-x-D/E motifs, which can be SUMOylated at three Lys residues, K46,<scene name='60/604477/Sumoylation/1'>K136</scene> and K244 <ref name="Terreni">PMID:20226045</ref>. | ||