6BSH

Structure of HIV-1 RT complexed with RNA/DNA hybrid in the RNA hydrolysis mode

Summary for 6BSH

• Entry DOI: 10.2210/pdb6bsh/pdb
• Descriptor: REVERSE TRANSCRIPTASE P66 SUBUNIT, REVERSE TRANSCRIPTASE P51 SUBUNIT, DNA (5'-D(*GP*TP*AP*TP*GP*CP*CP*AP*CP*TP*AP*GP*TP*TP*AP*TP*TP*GP*TP*GP*GP*CP*C)-3'), ... (9 entities in total)
• Functional Keywords: hiv-rt, dna-rna complex, rnase h, viral protein, viral protein-dna-rna complex, viral protein-dna-rna-inhibitor complex, viral protein/dna/rna/inhibitor
• Biological source: Human immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI); More
• Cellular location: Gag-Pol polyprotein: Host cell membrane ; Lipid-anchor. Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P03367
• Total number of polymer chains: 4
• Total formula weight: 131604.39

Authors

Tian, L.,Kim, M.,Yang, W. (deposition date: 2017-12-03, release date: 2018-01-03, Last modification date: 2024-05-22)

Primary citation

Tian, L.,Kim, M.S.,Li, H.,Wang, J.,Yang, W.
Structure of HIV-1 reverse transcriptase cleaving RNA in an RNA/DNA hybrid.
Proc. Natl. Acad. Sci. U.S.A., 115:507-512, 2018

PubMed 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-Å 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 Å. 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.

PubMed: 29295939
DOI: 10.1073/pnas.1719746115

Experimental method

X-RAY DIFFRACTION (2.649 Å)