Nitrophorins: Lipocalin-based heme proteins transporting nitric oxide

Nitrophorins 1-4 (NPs; NP1 to NP4) are salivary heme proteins secreted from the blood-sucking insect Rhodnius prolixus. NPs transfer nitric oxide (NO) to the victim, resulting in vasodilatation, sequester histamine, reducing host inflammation and immune response, and inhibit blood coagulation. The NP fold is based on an eight-stranded antiparallel β-barrel, typically observed in the lipocalin homology family, which hosts a heme group. Although NPs use the ferric heme to bind NO and histamine, they are unrelated to the six/eight α-helix (non)vertebrate hemoglobins, which bind NO preferentially to the ferrous heme, but do not bind histamine. Therefore, NPs and hemoglobins can be considered as an evolutionary experiment, where the heme group has been adapted to structurally different protein families to achieve similar function(s).