Journal Article

Small-angle X-ray scattering-derived structure of the HIV-1 5′ UTR reveals 3D tRNA mimicry

Musier-Forsyth, Karin, Cantara, William A., Jones, Christopher P., Olson, Erik D.

2014

Overview

The most conserved region of the HIV type 1 (HIV-1) genome, the ∼335-nt 5′ UTR, is characterized by functional stem loop domains responsible for regulating the viral life cycle. Despite the indispensable nature of this region of the genome in HIV-1 replication, 3D structures of multihairpin domains of the 5′ UTR remain unknown. Using small-angle X-ray scattering and molecular dynamics simulations, we generated structural models of the transactivation (TAR)/polyadenylation (polyA), primer-binding site (PBS), and Psi-packaging domains. TAR and polyA form extended, coaxially stacked hairpins, consistent with their high stability and contribution to the pausing of reverse transcription. The Psi domain is extended, with each stem loop exposed for interactions with binding partners. The PBS domain adopts a bent conformation resembling the shape of a tRNA in apo and primer-annealed states. These results provide a structural basis for understanding several key molecular mechanisms underlying HIV-1 replication.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: 5' Untranslated Regions - genetics / Annealing / Base Pairing / Base Sequence / Binding sites / Biological Sciences / Chromatography, Gel / genome / Genomes / HIV / HIV 1 / HIV-1 - chemistry / Human immunodeficiency virus / Human immunodeficiency virus 1 / Models, Molecular / molecular dynamics / Molecular Dynamics Simulation / Molecular Sequence Data / Packaging / Reverse transcription / RNA / RNA, Transfer - chemistry / Scattering, Small Angle / Simulation / Structural models / Three prime untranslated regions / transcriptional activation / Transfer RNA / Untranslated regions / Viral morphology / virus replication / X-radiation