Invited Lecture – Matthias Wolf

27 March 2024
IOCB Prague
Invited Lecture – Matthias Wolf

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


Cryo-EM Structure of the APOBEC3G-RNA Complex

Date and time

The lecture has been rescheduled for 27 March 2024, 10 a.m.


IOCB Prague, Lecture Hall


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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