2pnd

Structure or murine CRIg

spinqualitylabelsall models 2pnd, resolution 1.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2pnd is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Complement is an important component of the innate and adaptive immune response, yet complement split products generated through activation of each of the three complement pathways (classical, alternative, and lectin) can cause inflammation and tissue destruction. Previous studies have shown that complement activation through the alternative, but not classical, pathway is required to initiate antibody-induced arthritis in mice, but it is unclear if the alternative pathway (AP) plays a role in established disease. Previously, we have shown that human complement receptor of the immunoglobulin superfamily (CRIg) is a selective inhibitor of the AP of complement. Here, we present the crystal structure of murine CRIg and, using mutants, provide evidence that the structural requirements for inhibition of the AP are conserved in human and mouse. A soluble form of CRIg reversed inflammation and bone loss in two experimental models of arthritis by inhibiting the AP of complement in the joint. Our data indicate that the AP of complement is not only required for disease induction, but also disease progression. The extracellular domain of CRIg thus provides a novel tool to study the effects of inhibiting the AP of complement in established disease and constitutes a promising therapeutic with selectivity for a single complement pathway. A novel inhibitor of the alternative pathway of complement reverses inflammation and bone destruction in experimental arthritis.,Katschke KJ Jr, Helmy KY, Steffek M, Xi H, Yin J, Lee WP, Gribling P, Barck KH, Carano RA, Taylor RE, Rangell L, Diehl L, Hass PE, Wiesmann C, van Lookeren Campagne M J Exp Med. 2007 Jun 11;204(6):1319-25. Epub 2007 Jun 4. PMID:17548523 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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