RNA and related retro viruses persist to pose serious threats to human health and global economies. Disease progression mediated by viral pathogenesis requires numerous intersections between host proteins and viral RNA (vRNA) elements. Host-vRNA complexes drive essential processes in the replication cycles of viruses; as such, they represent untapped targets for therapeutic intervention. Members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family are cellular proteins often usurped by RNA viruses. The Tolbert lab studies the molecular mechanisms by which RNA viruses redirect hnRNPs to control viral gene expression. In this talk, Tolbert will describe solution NMR structures of conserved viral RNA elements that regulate splicing and translation. He further will show that conformational adaptation and slow protein motions are fundamental properties by which the cellular hnRNP protein achieve cognate RNA recognition. In new and exciting results, the lab described the NMR structure of a viral RNA-small molecule complex that inhibits viral replication by attenuating viral translation and shows that the small molecule inhibitor functions through a novel allosteric mechanism to increase the affinity of an RNA- protein complex. The collective knowledge this lab is producing suggests that protein- RNA cooperativity and mutual allostery manifest as idiosyncratic mechanisms that regulate viral gene expression.
About the Speaker:
Blanton S. Tolbert is a professor of chemistry at Case Western Reserve University, where he oversees a diverse research group that endeavors to understand biochemical mechanisms by which human pathogenic RNA viruses replicate within cells, and to leverage this knowledge to identify novel drug targets for therapeutic intervention. Tolbert is the PI of multiple NIH grants, and he has published in top journals including Nature Communications, the Proceedings of the National Academy of Sciences and the Journal of the American Chemical Society. Tolbert also serves on the NIH Office of AIDS Research Advisory Council (OARAC), and he will become the next chair of OARAC in 2021. He is a member of the Burroughs Wellcome Fund Postdoctoral Enrichment Program Advisory Board and an editor for the Journal of Biological Chemistry and Microbiology and Molecular Biology Reviews. Tolbert is the proud father of two boys, and in his spare time he enjoys exploring the outdoors in the Cleveland Metroparks.