Multiple ligand binding sites on domain seven of human complement factor H

Foreign particles and damaged host cells can activate the complement system leading to their destruction by the host defense system. Factor H (fH) pla ys 3 vital role in restricting complement activation on host cells through interactions with polyanions such as heparin, while allowing activation to proceed on foreign surfaces, Complement activation by damaged host cells is also down regulated by M. which is localized to injured areas through inte ractions with C-reactive protein (CRP). A number of pathogens have develope d mechanisms by which they can also bind M and thus exploit its protective properties. One such organism is Group A Streptococcus (GAS) which mediates fH binding via its surface expressed M-protein. fH consists of 20 conserved short consensus repeat (SCR) units and mutagene sis studies indicate that the seventh repeat is responsible for interaction s with heparin. CRP and M-protein. We recently performed molecular modellin g of M SCR 7 and identified a cluster of positively charged residues on one face of the domain. By alanine replacement mutagenesis, we demonstrated th at these residues are involved in heparin. CRP and M protein binding, which indicates that there is a common site within M SCR 7 responsible for multi ple ligand recognition. (C) 2001 Elsevier Science B.V. All rights reserved.