Perforin-2/Mpeg1 and other pore-forming proteins throughout evolution

Development of the ancient innate immune system required not only a mechanism to recognize foreign organisms from self but also to destroy them. Pore-forming proteins containing the membrane attack complex Perforin domain were one of the first triumphs of an innate immune system needing to eliminate microbes and virally infected cells. Membrane attack complex of complement and Perforin domain proteins is unique from other immune effector molecules in that the mechanism of attack is strictly physical and unspecific. The large water-filled holes created by membrane attack complex of complement and Perforin domain pore formation allow access for additional effectors to complete the destruction of the foreign organism via chemical or enzymatic attack. Perforin-2/macrophage-expressed protein 1 is one of the oldest membrane attack complexes of complement and Perforin domain protein involved in immune defense, and it is still functional today in vertebrates. Here, we trace the impact of Perforin-2/macrophage-expressed protein 1 from the earliest multicellular organisms to modern vertebrates, as well as review the development of other membrane attack complexes of complement and Perforin domain member proteins.