Structure of HIV-1 reverse transcriptase cleaving RNA in an RNA/DNA hybrid
SCIE
SCOPUS
- Title
- Structure of HIV-1 reverse transcriptase cleaving RNA in an RNA/DNA hybrid
- Authors
- Tian, Lan; KIM, MIN SUNG; Li, Hongzhi; Wang, Jimin; Yang, Wei
- Date Issued
- 2018-01
- Publisher
- NATL ACAD SCIENCES
- Abstract
- HIV-1 reverse transcriptase (RT) contains both DNA polymerase and RNase H activities to convert the viral genomic RNA to dsDNA in infected host cells. Here we report the 2.65-angstrom resolution structure of HIV-1 RT engaging in cleaving RNA in an RNA/DNA hybrid. A preferred substrate sequence is absolutely required to enable the RNA/DNA hybrid to adopt the distorted conformation needed to interact properly with the RNase H active site in RT. Substituting two nucleotides 4 bp upstream from the cleavage site results in scissile-phosphate displacement by 4 angstrom. We also have determined the structure of HIV-1 RT complexed with an RNase H-resistant polypurine tract sequence, which adopts a rigid structure and is accommodated outside of the nuclease active site. Based on this newly gained structural information and a virtual drug screen, we have identified an inhibitor specific for the viral RNase H but not for its cellular homologs.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/41007
- DOI
- 10.1073/pnas.1719746115
- ISSN
- 0027-8424
- Article Type
- Article
- Citation
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-PHYSICAL SCIENCES, vol. 115, no. 3, page. 507 - 512, 2018-01
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