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Factor H (FH) is an abundant regulator of complement activation and protects host cells from self-attack by complement. Here we provide insights into the regulatory activity of FH by solving the crystal structure of the first four domains of FH in complex with its target C3b. FH interacts with multiple domains of C3b, covering a large, extended surface(More)
The parallel expression of activation products of the coagulation, fibrinolysis, and complement systems has long been observed in both clinical and experimental settings. Several interconnections between the individual components of these cascades have also been described, and the list of shared regulators is expanding. The co-existence and interplay of(More)
Activation of the complement cascade induces inflammatory responses and marks cells for immune clearance. In the central complement-amplification step, a complex consisting of surface-bound C3b and factor B is cleaved by factor D to generate active convertases on targeted surfaces. We present crystal structures of the pro-convertase C3bB at 4 angstrom(More)
Activation of the complement system generates potent chemoattractants and opsonizes cells for immune clearance. Short-lived protease complexes cleave complement component C3 into anaphylatoxin C3a and opsonin C3b. Here we report the crystal structure of the C3 convertase formed by C3b and the protease fragment Bb, which was stabilized by the bacterial(More)
Compstatin is a 13-residue peptide that inhibits activation of the complement system by binding to the central component C3 and its fragments C3b and C3c. A combination of theoretical and experimental approaches has previously allowed us to develop analogs of the original compstatin peptide with up to 264-fold higher activity; one of these analogs is now in(More)
BACKGROUND Exposure of chondroitin sulfate A (CS-A) on the surface of activated platelets is well established. The aim of the present study was to investigate to what extent CS-A contributes to the binding of the complement recognition molecule C1q and the complement regulators C1 inhibitor (C1INH), C4b-binding protein (C4BP), and factor H to platelets. (More)
Activation of the thrombotic and complement systems is the main recognition and effector mechanisms in the multiple adverse biological responses triggered when biomaterials or therapeutic cells come into blood contact. We have created a surface which is auto-protective to human innate immunity by combining three fundamentally different strategies, all(More)
Background: Hydrogen/deuterium exchange detected by mass spectrometry (HDX-MS) is an experimental technique that provides valuable information about a protein's structure and dynamics. Data produced by HDX-MS experiments is often interpreted using a crystal structure of the protein. However, it has been suggested that more accurate interpretations can be(More)
Regulators of complement activation (RCA) inhibit complement-induced immune responses on healthy host tissues. We present crystal structures of human RCA (MCP, DAF, and CR1) and a smallpox virus homolog (SPICE) bound to complement component C3b. Our structural data reveal that up to four consecutive homologous CCP domains (i-iv), responsible for inhibition,(More)
Wound healing is a complex homeostatic response to injury that engages numerous cellular activities, processes, and cell-to-cell interactions. The complement system, an intricate network of proteins with important roles in immune surveillance and homeo-stasis, has been implicated in many physiological processes; however, its role in wound healing remains(More)