7LVA

Solution structure of the HIV-1 PBS-segment

Replaces:  7K1Z

Summary for 7LVA

• Entry DOI: 10.2210/pdb7lva/pdb
• NMR Information: BMRB: 30868
• Descriptor: RNA (103-MER) (1 entity in total)
• Functional Keywords: primer binding site, reverse transcription, rna
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 1
• Total formula weight: 33249.84

Authors

Heng, X.,Song, Z. (deposition date: 2021-02-24, release date: 2021-03-17, Last modification date: 2024-05-15)

Primary citation

Song, Z.,Gremminger, T.,Singh, G.,Cheng, Y.,Li, J.,Qiu, L.,Ji, J.,Lange, M.J.,Zuo, X.,Chen, S.J.,Zou, X.,Boris-Lawrie, K.,Heng, X.
The three-way junction structure of the HIV-1 PBS-segment binds host enzyme important for viral infectivity.
Nucleic Acids Res., 49:5925-5942, 2021

PubMed Abstract: HIV-1 reverse transcription initiates at the primer binding site (PBS) in the viral genomic RNA (gRNA). Although the structure of the PBS-segment undergoes substantial rearrangement upon tRNALys3 annealing, the proper folding of the PBS-segment during gRNA packaging is important as it ensures loading of beneficial host factors. DHX9/RNA helicase A (RHA) is recruited to gRNA to enhance the processivity of reverse transcriptase. Because the molecular details of the interactions have yet to be defined, we solved the solution structure of the PBS-segment preferentially bound by RHA. Evidence is provided that PBS-segment adopts a previously undefined adenosine-rich three-way junction structure encompassing the primer activation stem (PAS), tRNA-like element (TLE) and tRNA annealing arm. Disruption of the PBS-segment three-way junction structure diminished reverse transcription products and led to reduced viral infectivity. Because of the existence of the tRNA annealing arm, the TLE and PAS form a bent helical structure that undergoes shape-dependent recognition by RHA double-stranded RNA binding domain 1 (dsRBD1). Mutagenesis and phylogenetic analyses provide evidence for conservation of the PBS-segment three-way junction structure that is preferentially bound by RHA in support of efficient reverse transcription, the hallmark step of HIV-1 replication.

PubMed: 33978756
DOI: 10.1093/nar/gkab342

Experimental method

SOLUTION NMR
SOLUTION SCATTERING