Open Access
Scientific Reports, volume 7, issue 1, publication number 5649
Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting
Knyazhanskaya Ekaterina S
2
,
Zalevsky Artur O
1
,
Sizov Aleksander I
2
,
Zatsepin Timofei S.
2, 3
,
Publication type: Journal Article
Publication date: 2017-07-17
PubMed ID:
28717247
Multidisciplinary
Abstract
Human Ku70/Ku80 protein is known to influence HIV-1 replication. One of the possible reasons may be the protection of integrase from proteasomal degradation by Ku70 subunit. We demonstrated that recombinant HIV-1 integrase and Ku70 form a stable complex, while no interaction of Ku70 with integrase from prototype foamy virus was observed. By analyzing protein subdomains we determined two binding sites in the structure of both Ku70 and integrase: the 51–160 a.a. region of integrase interacts with residues 251–438 of Ku70, whereas Ku70 N-terminal domain (1–250 a.a.) contacts an α6-helix in the 200–220 a.a. integrase region. Single substitutions within integrase (E212A or L213A) block the interaction with Ku70 thus indicating that the binding site formed by the 200–220 a.a. integrase region is crucial for complex formation. E212A/L213A substitutions decreased the integrase capacity to bind Ku70 in HEK293T cells. A conjugate of 2′-ОMe-GGUUUUUGUGU oligonucleotide with eosin is shown by molecular modeling to shield integrase residues E212/L213 and is effective in blocking complex formation of Ku70 with integrase what makes the complex between α6-helix and Ku70(1–250) a possible target for drug development.
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Anisenko A. N. et al. Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting // Scientific Reports. 2017. Vol. 7. No. 1. 5649
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Anisenko A. N., Knyazhanskaya E. S., Zalevsky A. O., Agapkina J. Yu., Sizov A. I., Zatsepin T. S., Gottikh M. B. Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting // Scientific Reports. 2017. Vol. 7. No. 1. 5649
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TY - JOUR
DO - 10.1038/s41598-017-05659-5
UR - https://doi.org/10.1038%2Fs41598-017-05659-5
TI - Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting
T2 - Scientific Reports
AU - Anisenko, Andrey N
AU - Knyazhanskaya, Ekaterina S
AU - Zalevsky, Artur O
AU - Agapkina, Julia Yu
AU - Sizov, Aleksander I
AU - Zatsepin, Timofei S.
AU - Gottikh, Marina B.
PY - 2017
DA - 2017/07/17 00:00:00
PB - Springer Nature
IS - 1
VL - 7
PMID - 28717247
SN - 2045-2322
ER -
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@article{2017_Anisenko,
author = {Andrey N Anisenko and Ekaterina S Knyazhanskaya and Artur O Zalevsky and Julia Yu Agapkina and Aleksander I Sizov and Timofei S. Zatsepin and Marina B. Gottikh},
title = {Characterization of HIV-1 integrase interaction with human Ku70 protein and initial implications for drug targeting},
journal = {Scientific Reports},
year = {2017},
volume = {7},
publisher = {Springer Nature},
month = {jul},
url = {https://doi.org/10.1038%2Fs41598-017-05659-5},
number = {1},
doi = {10.1038/s41598-017-05659-5}
}