PAN domains have significant functional versatility fulfilling diverse biological roles by mediating protein-protein and protein-carbohydrate interactions. These domains contain a hair-pin loop like structure, similar to that found in knottins but with a different pattern of disulfide bonds.
It has been shown that the N-terminal domains of members of the plasminogen/hepatocyte growth factor family, the apple domains of the plasma prekallikrein/coagulation factor XI family, and domains of various nematode proteins belong to the same module superfamily, the PAN module. The PAN domain contains a conserved core of three disulfide bridges. In some members of the family there is an additional fourth disulfide bridge that links the N- and C-termini of the domain.
The apple domain, as well as other examples of the PAN domain, consists of seven ò-strands that fold into a curved antiparallel sheet cradling an ñ-helix. Two disulfide bonds lock the helix onto the central ò4 and ò5 strands, whereas a third connects the N- and C-termini of the domain. In the apple domain, the ò4âÂÂò5 loop and ò5âÂÂò6 crossover loop generate a small pocket on the opposite side of the sheet from the ñ-helix.
In native plasminogen the PAN domain is associated with five kringle domains. The interactions between the PAN domain and the kringles play a critical role in stabilising the quaternary complex of the native plasminogen;