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Contribution of intertwined loop to membrane association revealed by Zika virus full‐length NS 1 structure
Author(s) -
Xu Xiaoying,
Song Hao,
Qi Jianxun,
Liu Yuqian,
Wang Haiyuan,
Su Chao,
Shi Yi,
Gao George F
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201695290
Subject(s) - flavivirus , biology , zika virus , dengue fever , virology , microcephaly , dengue virus , virus , viral replication , pathogenesis , flaviviridae , antibody dependent enhancement , genetics , immunology , viral disease
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 ( NS 1), 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 NS 1, 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 NS 1 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.