Contribution of intertwined loop to membrane association revealed by Zika virus full‐length NS1 structure

• Xiaoying Xu ^[1] ; Hao Song ^[4] ; Jianxun Qi ^[2] ; Yuqian Liu ^[5] ; Haiyuan Wang ^[6] ; Chao Su ^[3] ; Yi Shi ^[7] ; George F Gao
  1. [1] University of Science and Technology of China

     University of Science and Technology of China

     China

     
  2. [2] University of Chinese Academy of Sciences

     University of Chinese Academy of Sciences

     China

     
  3. [3] China Agricultural University

     China Agricultural University

     China

     
  4. [4] 2 CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing China; 3 Research Network of Immunity and Health (RNIH) Beijing Institutes of Life Science Chinese Academy of Sciences Beijing China
  5. [5] 2 CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing China; 5 Institute of Health Sciences Anhui University Hefei China
  6. [6] 2 CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing China; 6 College of Animal Sciences and Technology Guangxi University Nanning China
  7. [7] 2 CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing China; 4 Savaid Medical School University of Chinese Academy of Sciences Beijing China; 8 Center for Influenza Research and Early‐warning (CASCIRE) Chinese Academy of Sciences Beijing China

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 35, Nº. 20, 2016, págs. 2170-2178
• Idioma: inglés
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• Resumen

  • The association of Zika virus (ZIKV) infections with microcephaly and neurological diseases has highlighted an emerging public health concern. Here, we report the crystal structure of the full‐length ZIKV nonstructural protein 1 (NS1), a major host‐interaction molecule that functions in flaviviral replication, pathogenesis, and immune evasion. Of note, a long intertwined loop is observed in the wing domain of ZIKV NS1, and forms a hydrophobic “spike”, which can contribute to cellular membrane association. For different flaviviruses, the amino acid sequences of the “spike” are variable but their common characteristic is either hydrophobic or positively charged, which is a beneficial feature for membrane binding. Comparative studies with West Nile and Dengue virus NS1 structures reveal conserved features, but diversified electrostatic characteristics on both inner and outer faces. Our results suggest different mechanisms of flavivirus pathogenesis and should be considered during the development of diagnostic tools.