Mol Immunol 2020 Dec 01;128:235-248. doi: 10.1016/j.molimm.2020.10.013.

Fish complement C8 evolution, functional network analyses, and the theoretical interaction between C8 alpha chain and CD59.

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Complement C8, as a main component of the membrane attack complex, has only been identified in vertebrates. C8 comprises three subunits encoded by individual genes: C8a (alpha chain), C8b (beta chain), and C8g (gamma chain). However, in fish, there have been limited studies on the evolutionary history and systematic function of C8. In the present study, phylogenetic analysis indicated the complete divergence of C8 genes in different fish species. Codon usage bias analysis revealed the evolutionary complexity of C8 genes. Selective pressure analysis found that C8 genes have been affected by negative selection during evolution. Sequence alignment identified the sites that are under selective pressure. The systematic functions of C8 were revealed by gene co-expression and protein-protein interaction (PPI) network analyses. Notably, gene ontology enrichment analysis suggested that C8 proteins in zebrafish function mainly in the neuroendocrine system. Protein structural comparisons showed that putative functional residues and domains were conserved between the C8 subunits of human and grass carp. A preliminary study on the theoretical interaction between C8a and CD59 was performed according to the simulated protein stereo structure. The first functionally-related site was absent in the simulated conformation of the grass carp (Ctenopharyngodon idella) C8a-CD59 protein complex. We speculated that Tyr63 is involved in the functional loss of CD59 binding. The docking of CD59 to four potential sites (Met390, Ser391, Leu392, and Val405) in grass carp C8a was analyzed. The results of the present study provide a deeper understanding of the evolution and function of fish complement C8.

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Genes referenced: mindy3