The RNase H Domain: Structure, Function and Mechanism
An essential step of proliferation of retroviruses and transposition of long terminal repeat-containing retrotransposons is conversion of their single-stranded RNA genome into integration-competent, double-stranded proviral DNA by the multifunctional reverse transcriptase (RT) (Gilboa et al. 1979). RT is an enzyme with two activities. RNA-dependent DNA polymerase activity is first used to synthesize minus (−) strand DNA from the positive-stranded RNA genome, resulting in an RNA/DNA replication intermediate. The RNA strand of these hybrids is degraded by the RNase H activity to allow DNA-dependent synthesis of (+) strand DNA. RNase H activity is used not only to nonspecifically remove the RNA but also to specifically generate and remove RNA primers required to initiate synthesis of both DNA strands. In this chapter, we describe the current understanding of the HIV RNase H domain and its cellular counterparts – RNases H1 – with particular focus on structural data which, together with biochemical and computational studies, have revealed a detailed picture of the mechanism of action of this important and clinically significant enzyme. We will also discuss how the RNase H domain functions in the context of the dimeric HIV-1 RT.
KeywordsMoloney Murine Leukemia Virus Strand Transfer Human RNase Cellular Counterpart Scissile Phosphate
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