2pnd
From Proteopedia
(New page: 200px<br /><applet load="2pnd" size="350" color="white" frame="true" align="right" spinBox="true" caption="2pnd, resolution 1.00Å" /> '''Structure or murine ...) |
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==Overview== | ==Overview== | ||
| - | Complement is an important component of the innate and adaptive immune | + | 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. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | 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 | + | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17548523 17548523] |
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: ig-like domain]] | [[Category: ig-like domain]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:31:13 2008'' |
Revision as of 16:31, 21 February 2008
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Structure or murine CRIg
Overview
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.
About this Structure
2PND is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
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
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