Complexes of HIV-1 RT and DNA/RNA hybrid reveal structure compatible with RNA degradation

Mikalai Lapkouski^1, Lan Tian² & Wei Yang²

¹Institute of Nanobiology and Structural Biology GCRC, Academy of Sciences of the Czech Republic, Nové Hrady, e-mail: lapkouski@nh.cas.cz

² Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Reverse transcriptase (RT) is a multifunctional enzyme used by retroviruses to transcribe their single-stranded RNA genome into double stranded DNA capable of integration into host cell chromosomes. Several crystal structures of human immunodeficiency virus type 1 (HIV-1) RT complexed with different DNA-RNA hybrid substrates were solved. Structures of polymerase and RNaseH active sites are described as well as a number of insights into mechanisms of polymerization and RNA degradation are presented. Interactions between RT and DNA-RNA hybrids are discussed in comparison with other structures of apo- and DNA-bound forms of RT. Also, presence of non-nucleoside reverse transcriptase inhibitors in some structures may help better understand the mechanisms of inhibition, which can be used to generate potent anti-AIDS agents that specifically target the HIV-1 RT.

Lapkouski M, Tian L, Miller JT, Le Grice SF, Yang W.; Nat Struct Mol Biol. 2013 Feb; 20 (2):230-6.