2icf
From Proteopedia
(New page: 200px<br /> <applet load="2icf" size="450" color="white" frame="true" align="right" spinBox="true" caption="2icf, resolution 4.10Å" /> '''CRIg bound to C3b''...) |
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| - | [[Image:2icf.gif|left|200px]]<br /> | + | [[Image:2icf.gif|left|200px]]<br /><applet load="2icf" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2icf" size=" | + | |
caption="2icf, resolution 4.10Å" /> | caption="2icf, resolution 4.10Å" /> | ||
'''CRIg bound to C3b'''<br /> | '''CRIg bound to C3b'''<br /> | ||
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| + | ==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. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2ICF is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG and CA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2ICF is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=AC1:Nag+Binding+Site+For+Residue+A+643'>AC1</scene>, <scene name='pdbsite=AC2:Nag+Binding+Site+For+Residue+A+644'>AC2</scene>, <scene name='pdbsite=AC3:Bma+Binding+Site+For+Residue+A+645'>AC3</scene>, <scene name='pdbsite=AC4:Nag+Binding+Site+For+Residue+B+5'>AC4</scene> and <scene name='pdbsite=AC5:Ca+Binding+Site+For+Residue+A+647'>AC5</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ICF 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: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: complement receptor]] | [[Category: complement receptor]] | ||
[[Category: crig]] | [[Category: crig]] | ||
| + | [[Category: immune system]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 13 08:17:40 2008'' |
Revision as of 06:17, 13 February 2008
|
CRIg bound to C3b
Contents |
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.
Disease
Known diseases associated with this structure: C3 deficiency OMIM:[120700], Macular degeneration, age-related, 9 OMIM:[120700]
About this Structure
2ICF is a Protein complex structure of sequences from Homo sapiens with and as ligands. Known structural/functional Sites: , , , and . 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 08:17:40 2008
Categories: Homo sapiens | Protein complex | Wiesmann, C. | CA | NAG | Alternate pathway | C3 | C3b | Complement | Complement receptor | Crig | Immune system
