PUBLICATION
Structural basis for receptor recognition and pore formation of a zebrafish aerolysin-like protein
- Authors
- Jia, N., Liu, N., Cheng, W., Jiang, Y.L., Sun, H., Chen, L.L., Peng, J., Zhang, Y., Ding, Y.H., Zhang, Z.H., Wang, X., Cai, G., Wang, J., Dong, M.Q., Zhang, Z., Wu, H., Wang, H.W., Chen, Y., Zhou, C.Z.
- ID
- ZDB-PUB-151230-10
- Date
- 2016
- Source
- EMBO reports 17(2): 235-48 (Journal)
- Registered Authors
- Keywords
- crystal structure, electron microscopy reconstruction, high‐mannose glycan, pore‐forming protein, vertebrate
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Bacterial Toxins/chemistry*
- Bacterial Toxins/metabolism
- Lectins/chemistry
- Lectins/metabolism
- Mannans/chemistry
- Mannans/metabolism
- Molecular Dynamics Simulation*
- Molecular Sequence Data
- Pore Forming Cytotoxic Proteins/chemistry*
- Pore Forming Cytotoxic Proteins/genetics
- Pore Forming Cytotoxic Proteins/metabolism*
- Protein Binding
- Protein Structure, Tertiary
- Zebrafish
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 26711430 Full text @ EMBO Rep.
Citation
Jia, N., Liu, N., Cheng, W., Jiang, Y.L., Sun, H., Chen, L.L., Peng, J., Zhang, Y., Ding, Y.H., Zhang, Z.H., Wang, X., Cai, G., Wang, J., Dong, M.Q., Zhang, Z., Wu, H., Wang, H.W., Chen, Y., Zhou, C.Z. (2016) Structural basis for receptor recognition and pore formation of a zebrafish aerolysin-like protein. EMBO reports. 17(2):235-48.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping