2i6q
From Proteopedia
(New page: 200px<br /> <applet load="2i6q" size="450" color="white" frame="true" align="right" spinBox="true" caption="2i6q, resolution 2.100Å" /> '''Complement compone...) |
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| - | [[Image:2i6q.gif|left|200px]]<br /> | + | [[Image:2i6q.gif|left|200px]]<br /><applet load="2i6q" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2i6q, resolution 2.100Å" /> | caption="2i6q, resolution 2.100Å" /> | ||
'''Complement component C2a'''<br /> | '''Complement component C2a'''<br /> | ||
==Overview== | ==Overview== | ||
| - | C2a provides the catalytic center to the convertase complexes of the | + | C2a provides the catalytic center to the convertase complexes of the classical and lectin-binding pathways of complement activation. We determined two crystal structures of full-length C2a, with and without a pseudo ligand bound. Both structures reveal a near-active conformation of the catalytic center of the serine protease domains, while the von Willebrand factor A-type domains display an intermediate activation state of helix alpha7 with an open, activated metal-ion-dependent adhesion site. The open adhesion site likely serves to enhance the affinity for the ligand C4b, similar to "inside-out" signaling in integrins. Surprisingly, the N-terminal residues of C2a are buried in a crevice near helix alpha7, indicative of a structural switch between C2 and C2a. Extended loops on the protease domain possibly envelop the protruding anaphylatoxin domain of the substrate C3. Together with a putative substrate-induced completion of the oxyanion hole, this may contribute to the high substrate specificity of the convertases. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2I6Q is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, MN and MLI as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Classical-complement-pathway_C3/C5_convertase Classical-complement-pathway C3/C5 convertase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.43 3.4.21.43] Full crystallographic information is available from [http:// | + | 2I6Q is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=MN:'>MN</scene> and <scene name='pdbligand=MLI:'>MLI</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Classical-complement-pathway_C3/C5_convertase Classical-complement-pathway C3/C5 convertase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.43 3.4.21.43] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I6Q OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Daha, M | + | [[Category: Daha, M R.]] |
[[Category: Gros, P.]] | [[Category: Gros, P.]] | ||
[[Category: Hemrika, W.]] | [[Category: Hemrika, W.]] | ||
| - | [[Category: Huizinga, E | + | [[Category: Huizinga, E G.]] |
| - | [[Category: Milder, F | + | [[Category: Milder, F J.]] |
| - | [[Category: Raaijmakers, H | + | [[Category: Raaijmakers, H C.A.]] |
| - | [[Category: Romijn, R | + | [[Category: Romijn, R A.]] |
[[Category: Roos, A.]] | [[Category: Roos, A.]] | ||
[[Category: Schouten, A.]] | [[Category: Schouten, A.]] | ||
| - | [[Category: Vandeputte, D | + | [[Category: Vandeputte, D A.A.]] |
[[Category: MLI]] | [[Category: MLI]] | ||
[[Category: MN]] | [[Category: MN]] | ||
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[[Category: von willebrand factor-a domain]] | [[Category: von willebrand factor-a domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:49:39 2008'' |
Revision as of 15:49, 21 February 2008
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Complement component C2a
Contents |
Overview
C2a provides the catalytic center to the convertase complexes of the classical and lectin-binding pathways of complement activation. We determined two crystal structures of full-length C2a, with and without a pseudo ligand bound. Both structures reveal a near-active conformation of the catalytic center of the serine protease domains, while the von Willebrand factor A-type domains display an intermediate activation state of helix alpha7 with an open, activated metal-ion-dependent adhesion site. The open adhesion site likely serves to enhance the affinity for the ligand C4b, similar to "inside-out" signaling in integrins. Surprisingly, the N-terminal residues of C2a are buried in a crevice near helix alpha7, indicative of a structural switch between C2 and C2a. Extended loops on the protease domain possibly envelop the protruding anaphylatoxin domain of the substrate C3. Together with a putative substrate-induced completion of the oxyanion hole, this may contribute to the high substrate specificity of the convertases.
Disease
Known diseases associated with this structure: C2 deficiency OMIM:[217000], Macular degeneration, age-related, reduced risk of OMIM:[217000]
About this Structure
2I6Q is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Classical-complement-pathway C3/C5 convertase, with EC number 3.4.21.43 Full crystallographic information is available from OCA.
Reference
Structure of complement component C2A: implications for convertase formation and substrate binding., Milder FJ, Raaijmakers HC, Vandeputte MD, Schouten A, Huizinga EG, Romijn RA, Hemrika W, Roos A, Daha MR, Gros P, Structure. 2006 Oct;14(10):1587-97. PMID:17027507
Page seeded by OCA on Thu Feb 21 17:49:39 2008
Categories: Classical-complement-pathway C3/C5 convertase | Homo sapiens | Single protein | Daha, M R. | Gros, P. | Hemrika, W. | Huizinga, E G. | Milder, F J. | Raaijmakers, H C.A. | Romijn, R A. | Roos, A. | Schouten, A. | Vandeputte, D A.A. | MLI | MN | NAG | Serine protease domain | Von willebrand factor-a domain
