The unique structure of the zebrafish TNF-α homotrimer

In the current study, zebrafish TNF-α1 (zTNF-α1) was crystallized, and the structure was analyzed. The zTNF-α1 trimer is composed of three monomers whose height and width are 50 Å and 60 Å, respectively. Compared with human TNF-α, zTNF-α1 shows only ~30% amino acid identity, the EF loop of each monomer lacks three amino acids, the CD loop is increased by four amino acids, and the AA'' loop is increased by one amino acid. In addition, an A″-β-chain is added to the zTNF-α1 monomer, forming two β-sheet layers with 6:5 β-chains. The top of the trimer is missing three amino acids and the inner coil because the EF loop seals the central hole at the top, forming a unique structure. In conclusion, the results elucidated the structure of the zTNF-α1 trimer, providing immunological knowledge for studying TNF-α function in the zebrafish animal model and structural information for exploring TNF-α family evolution.