Poster Presentation Lorne Infection and Immunity 2020

Structural basis for importin alpha 3 specificity of W proteins in Hendra and Nipah viruses. (#134)

Sofiya Tsimbalyuk 1 , Kate M Smith 1 , Megan 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

Seven human isoforms of importin α mediate nuclear import of cargo in a tissue- and isoform-specific manner. How nuclear import adaptors differentially interact with cargo harbouring the same nuclear localisation signal (NLS) remains poorly understood, as the NLS recognition region is highly conserved. Here, we provide a structural basis for the nuclear import specificity of W proteins in Hendra and Nipah viruses. We determine the structural interfaces of these cargo bound to importin α1 and α3, identifying a 2.4-fold more extensive interface and > 50-fold higher binding affinity for importin α3. Through the design of importin α1 and α3 chimeric and mutant proteins, together with structures of cargo-free importin α1 and α3 isoforms, we establish that the molecular basis of specificity resides in the differential positioning of the armadillo repeats 7 and 8. Overall, our study provides mechanistic insights into a range of important nucleocytoplasmic transport processes reliant on isoform adaptor specificity.