Structural basis for receptor recognition and pore formation of a zebrafish aerolysin‐like protein. (28th December 2015)

• Record Type: Journal Article
• Authors: Jia, Ning; Liu, Nan; Cheng, Wang; Jiang, Yong‐Liang; Sun, Hui; Chen, Lan‐Lan; Peng, Junhui; Zhang, Yonghui; Ding, Yue‐He; Zhang, Zhi‐Hui; Wang, Xuejuan; Cai, Gang; Wang, Junfeng; Dong, Meng‐Qiu; Zhang, Zhiyong; Wu, Hui; Wang, Hong‐Wei; Chen, Yuxing; Zhou, Cong‐Zhao
• Is Part Of: EMBO reports. Volume 17:Number 2(2016:Feb.)
• Page Start: 235
• Page End: 248
• Publication Date: 2015-12-28
• Subjects: crystal structure -- electron microscopy reconstruction -- high‐mannose glycan -- pore‐forming protein -- vertebrate; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201540851
• Languages: English
• ISSNs: 1469-221X

Abstract

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. Synopsis: This study presents the first structures of a vertebrate aerolysin‐like pore‐forming protein, Dln1, as a water‐soluble dimer and membrane‐bound octameric quasi‐pore. Pore formation involves a conformational change, which might be triggered by binding of the lectin module of Dln1 to mannan. The structures of the water‐soluble Dln1 dimer and membrane‐bound octameric quasi‐pore were determined by X‐ray crystallography and electron microscopy, respectively. The pore‐forming process by Dln1 is activated by a mechanism distinct from the previously characterized bacterial members. Dln1 and its homologs might function as novel defense molecules and are conserved in bony fishes and lamprey. Abstract : This study presents the first structures of a vertebrate aerolysin‐like pore‐forming protein, Dln1, as a water‐soluble dimer and membrane‐bound octameric quasi‐pore. Pore formation involves a conformational change, which might be triggered by binding of the lectin module of Dln1 to mannan.