Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 1, Issue 3, Pages 433-443Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S1567-5769(00)00040-0
Keywords
complement; factor H; streptococcal M-protein; C-reactive protein; heparin
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Foreign particles and damaged host cells can activate the complement system leading to their destruction by the host defense system. Factor H (fH) plays 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 interactions with C-reactive protein (CRP). A number of pathogens have developed 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 mutagenesis studies indicate that the seventh repeat is responsible for interactions with heparin. CRP and M-protein. We recently performed molecular modelling of M SCR 7 and identified a cluster of positively charged residues on one face of the domain. By alanine replacement mutagenesis, we demonstrated that 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 multiple ligand recognition. (C) 2001 Elsevier Science B.V. All rights reserved.
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