The unique structure of the zebrafish TNF-alpha homotrimer

In the current study, zebrafish TNF-alpha 1 (zTNF-alpha 1) was crystallized, and the structure was analyzed. The zTNF-alpha 1 trimer is composed of three monomers whose height and width are 50 angstrom and 60 angstrom, respectively. Compared with human TNF-alpha, zTNF-alpha 1 shows only similar to 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 ''-beta-chain is added to the zTNF-alpha 1 monomer, forming two beta-sheet layers with 6:5 beta-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-alpha 1 trimer, providing immunological knowledge for studying TNF-alpha function in the zebrafish animal model and structural information for exploring TNF-alpha family evolution.