title: Contribution of intertwined loop to membrane association revealed by Zika virus full-length NS1 structure.
abstract: 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.
authors: School of Life Sciences, University of Science and Technology of China, Hefei, China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors: Xiaoying
authors: X
authors: Xu
authors: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.|Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.
authors: Hao
authors: H
authors: Song
authors: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.|Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
authors: Jianxun
authors: J
authors: Qi
authors: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.|Institute of Health Sciences, Anhui University, Hefei, China.
authors: Yuqian
authors: Y
authors: Liu
authors: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.|College of Animal Sciences and Technology, Guangxi University, Nanning, China.
authors: Haiyuan
authors: H
authors: Wang
authors: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.|College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors: Chao
authors: C
authors: Su
authors: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China shiyi@im.ac.cn gaof@im.ac.cn.|Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.|Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing, China.
authors: Yi
authors: Y
authors: Shi
authors: School of Life Sciences, University of Science and Technology of China, Hefei, China shiyi@im.ac.cn gaof@im.ac.cn.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.|Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.|Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.|Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing, China.|National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China.
authors: George F
authors: 0000-0002-3869-615X
authors: GF
authors: Gao
mesh_terms: D003460:Crystallization; D011487:Protein Conformation; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics; D000071244:Zika Virus
chemical_list: C079340:NS1 protein, Dengue virus type 2; C100315:NS1 protein, Flavivirus; D017361:Viral Nonstructural Proteins; C531936:nonstructural protein 1, West Nile virus
keywords: NS1; Zika virus; crystal structure; membrane association