Title : Structure of complement component C2A: implications for convertase formation and substrate binding
Abstract :
- C2a provides the catalytic center to the convertase complexes of the classical and lectin-binding pathways of complement activation
- We determined two crystal structures of full-length C2a, with and without a pseudo ligand bound
- Both structures reveal a near-active conformation of the catalytic center of the serine protease domains , while the von Willebrand factor A-type domains display an intermediate activation state of helix alpha7 with an open, activated metal-ion-dependent adhesion site
- The open adhesion site likely serves to enhance the affinity for the ligand C4b , similar to "inside-out" signaling in integrins
- Surprisingly, the N-terminal residues of C2a are buried in a crevice near helix alpha7, indicative of a structural switch between C2 and C2a
- Extended loops on the protease domain possibly envelop the protruding anaphylatoxin domain of the substrate C3
- Together with a putative substrate-induced completion of the oxyanion hole, this may contribute to the high substrate specificity of the convertases