Complex of HIV-1 Integrase with Cellular Ku Protein: Interaction Interface and Search for Inhibitors

International Journal of Molecular Sciences

Marina Serebryakova¹  Andrey Anisenko²  Maria Khrenova²  Simon Galkin²  Marina Gottikh²  Ekaterina Ilgova² 

[1] Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia;Chemistry Department, Lomonosov Moscow State University, 119992 Moscow, Russia;

关键词: Ku70;    HIV-1;    integrase;    protein–protein interactions;   

DOI  :  10.3390/ijms23062908

来源: DOAJ

【 摘 要 】

The interaction of HIV-1 integrase and the cellular Ku70 protein is necessary for HIV replication due to its positive effect on post-integration DNA repair. We have previously described in detail the Ku70 binding site within integrase. However, the integrase binding site in Ku70 remained poorly characterized. Here, using a peptide fishing assay and site-directed mutagenesis, we have identified residues I72, S73, and I76 of Ku70 as key for integrase binding. The molecular dynamics studies have revealed a possible way for IN to bind to Ku70, which is consistent with experimental data. According to this model, residues I72 and I76 of Ku70 form a “leucine zipper” with integrase residues, and, therefore, their concealment by low-molecular-weight compounds should impede the Ku70 interaction with integrase. We have identified such compounds by molecular docking and have confirmed their capacity to inhibit the formation of the integrase complex with Ku70. Our data demonstrate that the site of IN binding within Ku70 identified in the present work may be used for further search for inhibitors of the integrase binding to Ku70.

【 授权许可】

Unknown