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

FIGIEL, M, Miroslav KREPL, J POZNANSKI, A GOTAB, Jiří ŠPONER a Marcin NOWOTNY. Coordination between the polymerase and RNase H activity of HIV-1 reverse transcriptase. Nucleic Acids Research. Oxford: Oxford University Press, 2017, roč. 45, č. 6, s. 3341-3352. ISSN 0305-1048. Dostupné z: https://dx.doi.org/10.1093/nar/gkx004.

Základní údaje

• Originální název: Coordination between the polymerase and RNase H activity of HIV-1 reverse transcriptase
• Autoři: FIGIEL, M, Miroslav KREPL, J POZNANSKI, A GOTAB, Jiří ŠPONER a Marcin NOWOTNY.
• Vydání: Nucleic Acids Research, Oxford, Oxford University Press, 2017, 0305-1048.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Utajení: není předmětem státního či obchodního tajemství
• WWW: URL
• Impakt faktor: Impact factor: 11.561
• Doi: http://dx.doi.org/10.1093/nar/gkx004
• UT WoS: 000398376200041
• Příznaky: Mezinárodní význam, Recenzováno

Anotace

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.