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| | {{STRUCTURE_2ice| PDB=2ice | SCENE= }} | | {{STRUCTURE_2ice| PDB=2ice | SCENE= }} |
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| - | '''CRIg bound to C3c'''
| + | ===CRIg bound to C3c=== |
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| - | ==Overview==
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| - | The complement system is a key part of the innate immune system, and is required for clearance of pathogens from the bloodstream. After exposure to pathogens, the third component of the complement system, C3, is cleaved to C3b which, after recruitment of factor B, initiates formation of the alternative pathway convertases. CRIg, a complement receptor expressed on macrophages, binds to C3b and iC3b mediating phagocytosis of the particles, but it is unknown how CRIg selectively recognizes proteolytic C3-fragments and whether binding of CRIg to C3b inhibits convertase activation. Here we present the crystal structure of C3b in complex with CRIg and, using CRIg mutants, provide evidence that CRIg acts as an inhibitor of the alternative pathway of complement. The structure shows that activation of C3 induces major structural rearrangements, including a dramatic movement (>80 A) of the thioester-bond-containing domain through which C3b attaches to pathogen surfaces. We show that CRIg is not only a phagocytic receptor, but also a potent inhibitor of the alternative pathway convertases. The structure provides insights into the complex macromolecular structural rearrangements that occur during complement activation and inhibition. Moreover, our structure-function studies relating the structural basis of complement activation and the means by which CRIg inhibits the convertases provide important clues to the development of therapeutics that target complement. | + | The line below this paragraph, {{ABSTRACT_PUBMED_17051150}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17051150 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17051150}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Crig]] | | [[Category: Crig]] |
| | [[Category: Immune system]] | | [[Category: Immune system]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:19:48 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:04:40 2008'' |
Revision as of 10:04, 27 July 2008
Template:STRUCTURE 2ice
CRIg bound to C3c
Template:ABSTRACT PUBMED 17051150
About this Structure
2ICE is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of C3b in complex with CRIg gives insights into regulation of complement activation., Wiesmann C, Katschke KJ, Yin J, Helmy KY, Steffek M, Fairbrother WJ, McCallum SA, Embuscado L, DeForge L, Hass PE, van Lookeren Campagne M, Nature. 2006 Nov 9;444(7116):217-20. Epub 2006 Oct 15. PMID:17051150
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