Structural basis for receptor recognition and pore formation of a zebrafish aerolysin-like protein

Ning Jia, Nan Liu, Wang Cheng, Yong Liang Jiang, Hui Sun, Lan Lan Chen, Junhui Peng, Yonghui Zhang, Yue He Ding, Zhi Hui Zhang, Xuejuan Wang, Gang Cai, Junfeng Wang, Meng Qiu Dong, Zhiyong Zhang, Hui Wu, Hong Wei Wang, Yuxing Chen, Cong Zhao Zhou

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)235-248
Number of pages14
JournalEMBO Reports
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

Keywords

  • crystal structure
  • electron microscopy reconstruction
  • high-mannose glycan
  • pore-forming protein
  • vertebrate

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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