Complement is an important part of human innate immunity and protects us against invading microbes. It consists of over 30 proteins on plasma and cell surfaces. Complement can activate via three different pathways (classical, lectin and alternative) and as a result of activation of all pathways target cell is opsonized e.g. marked for phagocytosis or directly lysed. During the activation anaphylatoxins released enhance inflammatory response. As a powerful system complement needs to be tightly regulated, and many proteins in plasma and cell surfaces are complement regulators. The main alternative pathway regulator in plasma is factor H (FH)

Our group has studied structural basis of target recognition by complement alternative pathway. We have solved the structure of the C-terminus of the main complement alternative pathway regulator factor H (FH) alone and together with its main ligand, C3d. These structures lead us to propose a model how FH recognizes targets and thus dictates, how alternative pathway activation of complement proceeds.

We have also analyzed in detail, how microbes utilize FH using a same, conserved binding site on FH C-terminus. We are interested in structures of microbial FH-binding proteins and further analysis of FH interactions with different ligands.