Zvaná přednáška – Matthias Wolf

26. března 2024
ÚOCHB
Zvaná přednáška – Matthias Wolf
Přednášející

Prof. Matthias Wolf (Okinawa Institute of Science and Technology, Graduate University, Okinawa, Japonsko)

Téma

Cryo-EM Structure of the APOBEC3G-RNA Complex

Datum a čas

Přednáška byla přeložena na 26. března 2024, 10:00

Místo

Přednáškový sál ÚOCHB

Abstrakt

Great effort has been devoted to discovering the basis of A3G-Vif interaction, the key event of HIV's counteraction mechanism to evade antiviral innate immune response. Here we show reconstitution of the A3G-Vif complex and subsequent A3G ubiquitination in vitro and report the cryo-EM structure of the A3G-Vif complex at 2.8 Å resolution using solubility-enhanced variants of A3G and Vif. We present an atomic model of the A3G-Vif interface, which assembles via known amino acid determinants. This assembly is not achieved by protein-protein interaction alone, but also involves RNA. The cryo-EM structure and in vitro ubiquitination assays identify an adenine/guanine base preference for the interaction and a unique Vif-ribose contact. This establishes the biological significance of an RNA ligand. Further assessment of interactions between A3G, Vif, and RNA ligands show that the A3G-Vif assembly and subsequent ubiquitination can be controlled by amino acid mutations at the interface or by polynucleotide modification, suggesting that a specific chemical moiety would be a promising pharmacophore to inhibit the A3G-Vif interaction.

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