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-Structure paper
タイトル | High-resolution view of HIV-1 reverse transcriptase initiation complexes and inhibition by NNRTI drugs. |
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ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 2500, Year 2021 |
掲載日 | 2021年5月4日 |
著者 | Betty Ha / Kevin P Larsen / Jingji Zhang / Ziao Fu / Elizabeth Montabana / Lynnette N Jackson / Dong-Hua Chen / Elisabetta Viani Puglisi / |
PubMed 要旨 | Reverse transcription of the HIV-1 viral RNA genome (vRNA) is an integral step in virus replication. Upon viral entry, HIV-1 reverse transcriptase (RT) initiates from a host tRNA primer bound to the ...Reverse transcription of the HIV-1 viral RNA genome (vRNA) is an integral step in virus replication. Upon viral entry, HIV-1 reverse transcriptase (RT) initiates from a host tRNA primer bound to the vRNA genome and is the target of key antivirals, such as non-nucleoside reverse transcriptase inhibitors (NNRTIs). Initiation proceeds slowly with discrete pausing events along the vRNA template. Despite prior medium-resolution structural characterization of reverse transcriptase initiation complexes (RTICs), higher-resolution structures of the RTIC are needed to understand the molecular mechanisms that underlie initiation. Here we report cryo-EM structures of the core RTIC, RTIC-nevirapine, and RTIC-efavirenz complexes at 2.8, 3.1, and 2.9 Å, respectively. In combination with biochemical studies, these data suggest a basis for rapid dissociation kinetics of RT from the vRNA-tRNA initiation complex and reveal a specific structural mechanism of nucleic acid conformational stabilization during initiation. Finally, our results show that NNRTIs inhibit the RTIC and exacerbate discrete pausing during early reverse transcription. |
リンク | Nat Commun / PubMed:33947853 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.8 - 3.1 Å |
構造データ | EMDB-22899, PDB-7kjv: EMDB-22900, PDB-7kjw: EMDB-22901, PDB-7kjx: |
化合物 | ChemComp-MG: ChemComp-BOG: ChemComp-EFZ: ChemComp-NVP: |
由来 |
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キーワード | viral protein/RNA / reverse transcriptase / RNA / protein-RNA complex / tRNA / polymerase / viral protein-RNA complex / VIRAL PROTEIN |