Summary
The sequence of a 900-nucleotide segment (encoding part of the reverse transcriptase, including the entire RNase H domain) of the pol gene of the murine leukaemia virus (MLV) amphotropic strain 4070A is presented. Alignment of the inferred 4070A RNase H amino acid sequence (157 residues) with other MLV RNase H sequences revealed only minor differences compared with the divergence between other retroviral and prokaryotic or eukaryotic RNase H sequences. Only 10 residues were invariant across the entire sample set, but secondary structure predictions for the enzymes from E. coli, yeast, human liver and diverse retroviruses (HIV, Rous sarcoma virus, foamy viruses) supported, in every case, the five β-strands (1 to 5) and four or five α-helices (A, B/C, D, E) that have been identified by crystallography in the RNase H domain of HIV-1 reverse transcriptase and in E. coli RNase H. In the case of MLV, analysis of the RNase H domain sequences inferred from 10 different strains (including the amphotropic 4070A) predicted all five α-helices (A–E), as well as β-strands 4 and 5. However, the N-terminal segment (residues 1–40) was predicted, without exception and with high probability, to fold uniquely into one (or two adjacent) α-helix(es) encompassing residues 13–37, instead of the three β-strands known to exist in the HIV-1 and E. coli enzymes. The unerring consistency between the known and predicted structures of the HIV-1 and E. coli enzymes, and the prediction of the same structural elements (including β-strands 1–3 within the N-terminal segment) for all other (non-MLV) RNase H proteins examined in this study, suggests that the N-terminal segment of the MLV RNase H domain assumes a conformation distinct from that of other retroviral and cellular RNase H molecules. An additional (sixth) β-strand was also predicted uniquely within the C-terminal region of foamy virus RNase H domains.
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Received January 13, 1999 Accepted May 27, 1999
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Ey, P., Freeman, N., Bela, B. et al. Sequence and comparative structural analysis of the murine leukaemia virus amphotropic strain 4070A RNase H domain. Arch. Virol. 144, 2185–2199 (1999). https://doi.org/10.1007/s007050050632
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DOI: https://doi.org/10.1007/s007050050632