Poster Presentation The 47th Lorne Conference on Protein Structure and Function 2022

Structural basis for importin alpha 3 specificity of W proteins in Hendra and Nipah viruses (#345)

Sofiya Tsimbalyuk 1 , Kate M Smith 1 , Meghan R edwards 2 , Emily M Cross 1 , Jyoti Batra 2 , Tatiana P Soares da Costa 3 , David Aragao 4 , Christopher F Basler 2 , Jade K Forwood 1
  1. Charles Sturt University, Wagga Wagga, NEW SOUTH WALES, Australia
  2. Center for Microbial Pathogenesis, Institute for Biomedical Sciences, Georgia State University, Atlanta, USA
  3. Department of Biochemistry and Genetics, La Trobe University, Melbourne , VIC, Australia
  4. Australian Synchrotron, Australian Nuclear Science and Technology Organisation, Melbourne, VIC, Australia

The significance and severity of the zoonotic pathogens and the potential spread among human population is perfectly demonstrated by current worldwide emergency state. HeV and NiV are recently emergent, zoonotic pathogens of the Henipavirus genus in the Paramyxoviridae family with high fatality (~ 60%) and morbidity rate. There is no current treatment available. Nucleocytoplasmic transport of the proteins is essential cellular process that mediates gene expression, cell differentiation and is commonly involved in diseases including virial infections and cancer. Henipavirus W protein has been demonstrated to antagonise innate antiviral defences by blocking interferon-induced gene expression and by preventing expression of type I IFNs, withnuclear localisation shown to be important for the latter function. Previous reports have demonstrated specificity of the importin α3 (IMP α3 ) adaptor for the NiV W protein, the basis for this specificity is unknown. W protein displaying steady-state nuclear localisation due to a C-terminally located NLS. Here, we establish key differences in the binding interface of W proteins with importin α1 and α3, providing insights into adaptor specificity. These insights extend our understanding of adaptor specificity and establish how important nuclear cargo proteins are imported in an isoform-specific manner providing basis for selective targeting.