Nudelman, I. | Search bioRxiv

bioRxiv2021

Comprehensive Structure and Functional Adaptations of the Yeast Nuclear Pore Complex

Nuclear Pore Complexes (NPCs) mediate the nucleocytoplasmic transport of macromolecules. Here we provide a structure of the yeast NPC in which the inner ring is resolved by cryo-EM at - helical resolution to show how flexible connectors tie together different structural and functional layers in the spoke. These connectors are targets for phosphorylation and regulated disassembly in cells with an open mitosis. Moreover, some nucleoporin pairs and karyopherins have similar interaction motifs, which suggests an evolutionary and mechanistic link between assembly and transport. We also provide evidence for three major NPC variants that foreshadow functional specializations at the nuclear periphery. Cryo-electron tomography extended these studies to provide a comprehensive model of the in situ NPC with a radially-expanded inner ring. Our model reveals novel features of the central transporter and nuclear basket, suggests a role for the lumenal ring in restricting dilation and highlights the structural plasticity required for transport by the NPC.

biophysics↗

bioRxiv2021

Comparing host module activation patterns and temporal dynamics in infection by influenza H1N1 viruses

Influenza is a serious global health threat that shows varying pathogenicity among different virus strains. Understanding similarities and differences among activated functional pathways in the host responses can help elucidate therapeutic targets responsible for pathogenesis. To compare the types and timing of functional modules activated in host cells by four influenza viruses of varying pathogenicity, we developed a new DYNAmic MOdule (DYNAMO) method that addresses the need to compare functional module utilization over time. This integrative approach overlays whole genome time series expression data onto an immune-specific functional network, and extracts conserved modules exhibiting either different temporal patterns or overall transcriptional activity. We identified a common core response to influenza virus infection that is temporally shifted for different viruses. We also identified differentially regulated functional modules that reveal unique elements of responses to different virus strains. Our work highlights the usefulness of combining time series gene expression data with a functional interaction map to capture temporal dynamics of the same cellular pathways under different conditions. Our results help elucidate conservation of the immune response both globally and at a granular level, and provide mechanistic insight into the differences in the host response to infection by influenza strains of varying pathogenicity.

bioinformatics↗