2icc
From Proteopedia
(New page: 200px<br /> <applet load="2icc" size="450" color="white" frame="true" align="right" spinBox="true" caption="2icc, resolution 1.200Å" /> '''Extracellular Doma...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2icc.gif|left|200px]]<br /> | + | [[Image:2icc.gif|left|200px]]<br /><applet load="2icc" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2icc" size=" | + | |
caption="2icc, resolution 1.200Å" /> | caption="2icc, resolution 1.200Å" /> | ||
'''Extracellular Domain of CRIg'''<br /> | '''Extracellular Domain of CRIg'''<br /> | ||
| + | |||
| + | ==Overview== | ||
| + | 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. | ||
==About this Structure== | ==About this Structure== | ||
| - | 2ICC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 2ICC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ICC 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17051150 17051150] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 12: | Line 17: | ||
[[Category: complement receptor]] | [[Category: complement receptor]] | ||
[[Category: ig like domain]] | [[Category: ig like domain]] | ||
| + | [[Category: immune system]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 13 08:17:37 2008'' |
Revision as of 06:17, 13 February 2008
|
Extracellular Domain of CRIg
Overview
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.
About this Structure
2ICC is a Single protein structure of sequence 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
Page seeded by OCA on Wed Feb 13 08:17:37 2008
