Metal binding study of calreticulin: An immunomodulatory protein of human filarial parasite Brugia malayi.

Calreticulin (CRT), a highly conserved ubiquitous eukaryotic protein with a molecular mass of 46 kDa, containing three domains (N, P, and C) is involved in promoting prolonged parasite-host relations. Brugia malayi Calreticulin (BmCRT) is involved in the establishment of parasite infection by suppression of C1q-mediated host immune response. Calcium plays important role in this immunomodulatory mechanism of BmCRT. In the present study binding of calcium with BmCRT region involved in this interaction was investigated and correlated with the accompanying changes in fluorescence, circular dichroism (CD) and UV absorption. The results obtained clearly indicated that BmCRT is a calcium binding protein and contains types two of Ca2+ binding sites, one high affinity Ca2+ binding site at P domain and another low affinity Ca2+ binding site at C domain. Zinc also binds to additional sites that do not have appreciable affinity for the calcium. These studies have provided new knowledge that allows us to describe how the structure of BmCRT responds to interactions with calcium and zinc which is different from human CRT and also discuss how this mechanism help to complex formation with host C1q.