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Coordination between the polymerase and RNase H activity of HIV-1 reverse transcriptase

Figiel, Małgorzata and Krepl, Miroslav and Poznański, Jarosław and Gołąb, Agnieszka and Šponer, Jiří and Nowotny, Marcin (2017) Coordination between the polymerase and RNase H activity of HIV-1 reverse transcriptase. Nucleic Acids Research, 45 (6). pp. 3341-3352. ISSN 0305-1048

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Official URL: http://doi.org/10.1093/nar/gkx004


Replication of human immunodeficiency virus 1 (HIV-1) involves conversion of its single-stranded RNA genome to double-stranded DNA, which is integrated into the genome of the host. This conversion is catalyzed by reverse transcriptase (RT), which possesses DNA polymerase and RNase H domains. The available crystal structures suggest that at any given time the RNA/DNA substrate interacts with only one active site of the two domains of HIV-1 RT. Unknown is whether a simultaneous interaction of the substrate with polymerase and RNase H active sites is possible. Therefore, the mechanism of the coordination of the two activities is not fully understood. We performed molecular dynamics simulations to obtain a conformation of the complex in which the unwound RNA/DNA substrate simultaneously interacts with the polymerase and RNase H active sites. When the RNA/DNA hybrid was immobilized at the polymerase active site, RNase H cleavage occurred, experimentally verifying that the substrate can simultaneously interact with both active sites. These findings demonstrate the existence of a transient conformation of the HIV-1 RT substrate complex, which is important for modulating and coordinating the enzymatic activities of HIV-1 RT.

Item Type:Article
Subjects:Q Science > Q Science (General)
Divisions:Department of Biophysics
ID Code:1328
Deposited By: Prof Jaroslaw Poznanski
Deposited On:21 Apr 2017 08:45
Last Modified:21 Apr 2017 08:45

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