Structural models predict a significantly higher binding affinity between the NblA protein of cyanophage Ma-LMM01 and the phycocyanin of Microcystis aeruginosa NIES-298 compared to the host homolog

Abstract

Horizontal gene transfer events between viruses and hosts are widespread across the virosphere. In cyanophage-host systems, such events often involve the transfer of genes involved in photosynthetic processes. The genome of the lytic cyanomyovirus Ma-LMM01 infecting the toxic, bloom-forming, freshwater Microcystis aeruginosa NIES-298 contains a homolog of the non-bleaching A (nblA) gene, which was probably acquired from its host. The function of the NblA protein is to disassemble phycobilisomes, cyanobacterial light harvesting complexes that can comprise up to half of the cellular soluble protein content. NblA thus plays an essential dual role in cyanobacteria: it protects the cell from high light intensities and increases the intracellular nitrogen pool under nutrient limitation. NblA has previously been shown to interact with phycocyanin, one of the main components of phycobilisomes. Using structural modeling and protein-protein docking, we show that the NblA dimer of Ma-LMM01 is predicted to have a significantly higher binding affinity for M. aeruginosa NIES-298 phycocyanin ({beta})6 hexamers, compared to the host homolog. Protein-protein docking suggests that the viral NblA structural model is able to bind deeper into the phycocyanin groove. The main structural difference between the virus and host NblA appears to be an additional -helix near the N-terminus of the viral NblA, which could be partly responsible for the deeper binding into phycocyanin. This unique helical region, absent in the cellular NblA, would be expected to constitute a viral evolutionary innovation. We propose that a higher binding affinity of NblA to the host phycocyanin may represent a selective advantage for the virus, whose rapid infection cycle requires an increased phycobilisome degradation rate that is not fulfilled by the NblA of the host.