An investigation of the structure of tumour necrosis factor a in Cyprinus carpio

Abstract

Tumour necrosis factor a (TNF-a) is a soluble cytokine that has a number of different roles in the immune system. It carries out these functions by binding to one of its receptors TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2). Cyprinus carpio (common carp) is an economically important fish found in Europe and East Asia. Although TNF-a has been found to affect the immune system, its exact structure and function is not known. Knowledge of the structure could help in research into the function of TNF-a in common carp and fish in general.
The four isoforms of TNF-a in common carp are all highly conserved in amino acid sequence when aligned with each other, suggesting a very similar structure and function. TNF-a4 had an extended protein sequence at the C-terminal end, however, this did not affect the alignment. When aligned with TNF-a from humans and mice, several conserved residues were found to affect structure and function in human TNF-a. This was also seen in the alignment of TNF-a from common carp with other species of fish and mammals. A clustering of conserved residues, where structural elements of TNF-a of humans existed, was also observed. The prediction of secondary structure in TNF-a of common carp was very similar to that of TNF-a in humans and mice. The size, position and number of ß-strands in the predicted structure was similar to the known structures. However, no a-helices had been predicted, other than in TNF-a4. These results may contribute to the determination of the structure of TNF-a in common carp, which can lead to further research into its function in fish.