6B19

Architecture of HIV-1 reverse transcriptase initiation complex core

Summary for 6B19

• Entry DOI: 10.2210/pdb6b19/pdb
• Related: 1RTD 3V81
• EMDB information: 7031 7032
• Descriptor: reverse transcriptase p66 subunit, reverse transcriptase p51 subunit, RNA genome fragment, ... (4 entities in total)
• Functional Keywords: reverse transcriptase, trna, hiv-1, reverse transcription, rna, transcription, complex, rna-binding protein, backbone model, viral protein-rna complex, viral protein/rna
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 4
• Total formula weight: 174487.75

Authors

Larsen, K.P.,Mathiharan, Y.K.,Chen, D.H.,Puglisi, J.D.,Skiniotis, G.,Puglisi, E.V. (deposition date: 2017-09-18, release date: 2018-04-25, Last modification date: 2024-03-13)

Primary citation

Larsen, K.P.,Mathiharan, Y.K.,Kappel, K.,Coey, A.T.,Chen, D.H.,Barrero, D.,Madigan, L.,Puglisi, J.D.,Skiniotis, G.,Puglisi, E.V.
Architecture of an HIV-1 reverse transcriptase initiation complex.
Nature, 557:118-122, 2018

PubMed Abstract: Reverse transcription of the HIV-1 RNA genome into double-stranded DNA is a central step in viral infection and a common target of antiretroviral drugs . The reaction is catalysed by viral reverse transcriptase (RT) that is packaged in an infectious virion with two copies of viral genomic RNA each bound to host lysine 3 transfer RNA (tRNA), which acts as a primer for initiation of reverse transcription. Upon viral entry into cells, initiation is slow and non-processive compared to elongation. 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 tRNA 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.

PubMed: 29695867
DOI: 10.1038/s41586-018-0055-9

Experimental method

ELECTRON MICROSCOPY (4.5 Å)