Structural basis for receptor recognition and pore formation of a zebrafish aerolysin-like protein
Ning Jia1Nan Liu2Wang Cheng1Yong-Liang Jiang1Hui Sun1Lan-Lan Chen1Junhui Peng1Yonghui Zhang1Yue-He Ding3Zhi-Hui Zhang1Xuejuan Wang1Gang Cai1Junfeng Wang4Meng-Qiu Dong3Zhiyong Zhang1Hui Wu5Hong-Wei Wang2Yuxing Chen1Cong-Zhao Zhou1
1. Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China2. Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University3. National Institute of Biological Sciences4. High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences5. Department of Pediatric Dentistry and Microbiology, University of Alabama at Birmingham, Schools of Dentistry and Medicine
摘要：Various aerolysin-like pore-forming proteins have been identified from bacteria to vertebrates. However, mechanisms of receptor recognition and/or pore formation of the eukaryotic members remain unknown. Here we present the first couple of 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 towards high-mannose glycans triggers drastic conformational changes of the aerolysin module in a p H-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.