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

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 cyanophage Ma-LMM01 infecting the toxic, bloom-forming, freshwater NIES-298 contains a homolog of the () gene, which was probably transferred from a cyanobacterial 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 NIES-298 phycocyanin (αβ) 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 α-helix near the N-terminus of the viral NblA, which interacts with the inside of the phycocyanin groove and could thus be considered partly responsible for this deeper binding. Interestingly, phylogenetic analyses indicate that this longer was probably acquired from a different host. Based on infection experiments and previous findings, we propose that a higher binding affinity of the viral NblA to the host phycocyanin may represent a selective advantage for the virus, whose infection cycle requires an increased phycobilisome degradation rate that is not fulfilled by the NblA of the host.