Functional oligomeric state of avian sarcoma virus integrase |
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Authors: | Bao Kogan K Wang Hong Miller Jamie K Erie Dorothy A Skalka Anna Marie Wong Isaac |
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Affiliation: | Department of Biochemistry and Biophysics, Oregon State University, Oregon 97331, USA. |
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Abstract: | Retroviral integrase, one of only three enzymes encoded by the virus, catalyzes the essential step of inserting a DNA copy of the viral genome into the host during infection. Using the avian sarcoma virus integrase, we demonstrate that the enzyme functions as a tetramer. In presteady-state active site titrations, four integrase protomers were required for a single catalytic turnover. Volumetric determination of integrase-DNA complexes imaged by atomic force microscopy during the initial turnover additionally revealed substrate-induced assembly of a tetramer. These results suggest that tetramer formation may be a requisite step during catalysis with ramifications for antiviral design strategies targeting the structurally homologous human immunodeficiency virus, type 1 (HIV-1) integrase. |
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