CFP Human

Properdin was discovered over 50 years ago and was initially thought to act similarly to antibodies in the classical pathway of the complement system . However, this concept was later revised. Properdin is now understood to enhance complement activation by stabilizing the C3bBb convertase complex, which is essential for the amplification of the complement response .

Properdin binds to surfaces where C3b is deposited, such as bacterial cell walls or dying human cells. This binding promotes the formation and prolongs the lifetime of the C3bBb enzyme complexes, which convert C3 into C3b, thereby enhancing the complement-amplification loop . Properdin occurs as dimers, trimers, and tetramers in human plasma, which allows it to effectively recognize and bind to C3b-deposited surfaces .

Recent studies have provided detailed structural insights into properdin. Crystal structures of monomerized properdin have revealed ring-shaped arrangements formed by interactions between thrombospondin type-I repeat (TSR) domains . These structures suggest a mechanistic model in which properdin domains bridge interactions between C3b and factor B or its fragment Bb, enhancing the formation and stabilization of C3bBb convertases .

Properdin plays a significant role in various inflammatory diseases where there is excessive activation of the complement system. For example, in conditions like paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), properdin is essential for complement amplification . Inhibiting properdin has shown promise in preventing hemolysis of red blood cells and complement activation on endothelial cells in these diseases .

Human recombinant properdin is produced using recombinant DNA technology, which allows for the production of properdin in a controlled laboratory environment. This recombinant form is used in research and therapeutic applications to study and potentially treat diseases involving the complement system.