Summary information and primary citation
- PDB-id
- 6b19; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- viral protein-RNA
- Method
- cryo-EM (4.5 Å)
- Summary
- Architecture of hiv-1 reverse transcriptase initiation complex core
- Reference
- Larsen KP, Mathiharan YK, Kappel K, Coey AT, Chen DH, Barrero D, Madigan L, Puglisi JD, Skiniotis G, Puglisi EV (2018): "Architecture of an HIV-1 reverse transcriptase initiation complex." Nature, 557, 118-122. doi: 10.1038/s41586-018-0055-9.
- Abstract
- Reverse transcription of the HIV-1 RNA genome into double-stranded DNA is a central step in viral infection 1 and a common target of antiretroviral drugs 2 . The reaction is catalysed by viral reverse transcriptase (RT)3,4 that is packaged in an infectious virion with two copies of viral genomic RNA 5 each bound to host lysine 3 transfer RNA (tRNALys3), which acts as a primer for initiation of reverse transcription6,7. Upon viral entry into cells, initiation is slow and non-processive compared to elongation8,9. Despite extensive efforts, the structural basis of RT function during initiation has remained a mystery. Here we use cryo-electron microscopy to determine a three-dimensional structure of an HIV-1 RT initiation complex. In our structure, RT is in an inactive polymerase conformation with open fingers and thumb and with the nucleic acid primer-template complex shifted away from the active site. The primer binding site (PBS) helix formed between tRNALys3 and HIV-1 RNA lies in the cleft of RT and is extended by additional pairing interactions. The 5' end of the tRNA refolds and stacks on the PBS to create a long helical structure, while the remaining viral RNA forms two helical stems positioned above the RT active site, with a linker that connects these helices to the RNase H region of the PBS. Our results illustrate how RNA structure in the initiation complex alters RT conformation to decrease activity, highlighting a potential target for drug action.
