Journal article

Transitional changes in the CRP structure lead to the exposure of proinflammatory binding sites

David Braig, Tracy L Nero, Hans-Georg Koch, Benedict Kaiser, Xiaowei Wang, Jan R Thiele, Craig J Morton, Johannes Zeller, Jurij Kiefer, Lawrence A Potempa, Natalie A Mellett, Luke A Miles, Xiao-Jun Du, Peter J Meikle, Markus Huber-Lang, G Bjoern Stark, Michael W Parker, Karlheinz Peter, Steffen U Eisenhardt



C-reactive protein (CRP) concentrations rise in response to tissue injury or infection. Circulating pentameric CRP (pCRP) localizes to damaged tissue where it leads to complement activation and further tissue damage. In-depth knowledge of the pCRP activation mechanism is essential to develop therapeutic strategies to minimize tissue injury. Here we demonstrate that pCRP by binding to cell-derived microvesicles undergoes a structural change without disrupting the pentameric symmetry (pCRP*). pCRP* constitutes the major CRP species in human-inflamed tissue and allows binding of complement factor 1q (C1q) and activation of the classical complement pathway. pCRP*-microvesicle complexes lead to e..

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Awarded by German Research Foundation (DFG)

Funding Acknowledgements

This work was supported by a grant from the National Health and Medical Research Council of Australia (NHMRC) to K.P. and grants from the German Research Foundation (DFG) to S.U.E. (EI 866/1-1, EI 866/2-1, and EI 866/5-1), M. H.-L. (EI 866/5-1) and H.-G.K. (EI 866/2-1). Funding from the Victorian Government Operational Infrastructure Support Scheme to Baker IDI and St Vincent's Institute is acknowledged. S.U.E. holds a Heisenberg fellowship of the German Research Foundation (DFG) (EI 866/4-1) and has been granted a Heisenberg professorship. X.W. is an Australian Heart Foundation Fellow, X.J.D., P.A.M., M.W.P. and K.P. are NHMRC Research Fellows.