The crystal structure of the monomeric reverse transcriptase from Moloney murine leukemia virus

Structure. 2004 May;12(5):819-29. doi: 10.1016/j.str.2004.02.032.


Reverse transcriptases (RTs) are multidomain enzymes of variable architecture that couple both RNA- and DNA-directed DNA polymerase activities with an RNase H activity specific for an RNA:DNA hybrid in order to replicate the single-stranded RNA genome of the retrovirus. Previous structural work has been reported for the heterodimeric HIV-1 and HIV-2 RTs. We now report the first crystal structure of the full-length Moloney murine leukemia virus (MMLV) RT at 3.0 A resolution. The structure reveals a clamp-shaped molecule resulting from the relative positions of the thumb, connection, and RNase H domains that is strikingly different from the HIV-1 RT and provides the first example of a monomeric reverse transcriptase. A comparative analysis with related DNA polymerases suggests a unique trajectory for the template-primer exiting the polymerase active site and provides insights regarding processive DNA synthesis by MMLV RT.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Conserved Sequence
  • Crystallization
  • HIV-1 / chemistry
  • HIV-1 / enzymology
  • Molecular Sequence Data
  • Moloney murine leukemia virus / chemistry
  • Moloney murine leukemia virus / enzymology*
  • Protein Structure, Tertiary
  • RNA-Directed DNA Polymerase / chemistry*
  • Sequence Alignment


  • RNA-Directed DNA Polymerase

Associated data

  • PDB/1RW3