The crystal structure of the monomeric reverse transcriptase from Moloney murine leukemia virus.
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.
Das
Debanu
D
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202 USA.
Georgiadis
Millie M
MM
D000595:Amino Acid Sequence; D017124:Conserved Sequence; D003460:Crystallization; D015497:HIV-1 / Q000737:chemistry / Q000201:enzymology; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000737:chemistry / Q000201:enzymology*; D017434:Protein Structure, Tertiary; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry*; D016415:Sequence Alignment
D012194:RNA-Directed DNA Polymerase