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Structural basis for receptor recognition and pore formation of a zebrafish aerolysin‐like protein
Author(s) -
Jia Ning,
Liu Nan,
Cheng Wang,
Jiang YongLiang,
Sun Hui,
Chen LanLan,
Peng Junhui,
Zhang Yonghui,
Ding YueHe,
Zhang ZhiHui,
Wang Xuejuan,
Cai Gang,
Wang Junfeng,
Dong MengQiu,
Zhang Zhiyong,
Wu Hui,
Wang HongWei,
Chen Yuxing,
Zhou CongZhao
Publication year - 2016
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201540851
Subject(s) - aerolysin , zebrafish , computational biology , biology , basis (linear algebra) , receptor , microbiology and biotechnology , neuroscience , genetics , gene , mathematics , geometry , virulence
Abstract Various aerolysin‐like pore‐forming proteins have been identified from bacteria to vertebrates. However, the mechanism of receptor recognition and/or pore formation of the eukaryotic members remains unknown. Here, we present the first crystal and electron microscopy structures of a vertebrate aerolysin‐like protein from Danio rerio , termed Dln1, before and after pore formation. Each subunit of Dln1 dimer comprises a β‐prism lectin module followed by an aerolysin module. Specific binding of the lectin module toward high‐mannose glycans triggers drastic conformational changes of the aerolysin module in a pH ‐dependent manner, ultimately resulting in the formation of a membrane‐bound octameric pore. Structural analyses combined with computational simulations and biochemical assays suggest a pore‐forming process with an activation mechanism distinct from the previously characterized bacterial members. Moreover, Dln1 and its homologs are ubiquitously distributed in bony fishes and lamprey, suggesting a novel fish‐specific defense molecule.