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2aty

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Revision as of 09:30, 12 October 2017

Complement receptor chimaeric conjugate CR2-Ig

Structural highlights

2aty is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1igy, 1ghq, 1w2r
Gene:	Ighg1, Igh-4 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CR2_HUMAN] Genetic variations in CR2 are associated with susceptibility to systemic lupus erythematosus type 9 (SLEB9) [MIM:610927]. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a complex genetic basis. SLE is an inflammatory, and often febrile multisystemic disorder of connective tissue characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system.^[1] Defects in CR2 are the cause of immunodeficiency, common variable, type 7 (CVID7) [MIM:614699]. A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B cells is usually in the normal range, but can be low.^[2]

Function

[CR2_HUMAN] Receptor for complement C3Dd, for the Epstein-Barr virus on human B-cells and T-cells and for HNRPU. Participates in B lymphocytes activation.^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Complement receptor 2 (CR2; CD21) is a membrane-bound regulator of complement activation, being comprised of 15 or 16 short complement repeat (SCR) domains. A recombinant glycosylated human CR2 SCR 1-2 domain pair was engineered with the Fc fragment of a mouse IgG1 antibody to create a chimaera CR2-Ig containing the major ligand binding domains. Such a chimaera has therapeutic potential as a complement inhibitor or immune modulator. X-ray and neutron scattering and analytical ultracentrifugation identified its domain structure in solution, and provided a comparison with controversial folded-back crystal structures for deglycosylated CR2 SCR 1-2. The radius of gyration R(G) of CR2-Ig was determined to be 5.39(+/-0.14) nm and 5.29(+/-0.01) nm by X-ray and neutron scattering, respectively. The maximum dimension of CR2-Ig was determined to be 17 nm. The molecular mass of CR2-Ig ranged between 101,000 Da and 107,000 Da as determined by neutron scattering and sedimentation equilibrium, in good agreement with the sequence-derived value of 106,600 Da. Sedimentation velocity gave a sedimentation coefficient of 4.49(+/-0.11) S. Stereochemically complete models for CR2-Ig were constructed from crystal structures for the CR2 SCR 1-2 and mouse IgG1 Fc fragments. The two SCR domains and the Fc fragment were joined by randomised conformational peptides. The analysis of 35,000 possible CR2-Ig models showed that only those models in which the two SCR domains were arranged in an open V-shape in random orientations about the Fc fragment accounted for the scattering and sedimentation data. It was not possible to define one single conformational family of Fab-like fragment relative to the Fc fragment. This flexibility is attributed to the relatively long linker sequence and the absence of the antibody light chain from CR2-Ig. The modelling also confirmed that the structure of CR2 SCR 1-2 is more extended in solution than in its crystal structure.

Extended flexible linker structures in the complement chimaeric conjugate CR2-Ig by scattering, analytical ultracentrifugation and constrained modelling: implications for function and therapy.,Gilbert HE, Aslam M, Guthridge JM, Holers VM, Perkins SJ J Mol Biol. 2006 Feb 17;356(2):397-412. Epub 2005 Dec 5. PMID:16375923^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wu H, Boackle SA, Hanvivadhanakul P, Ulgiati D, Grossman JM, Lee Y, Shen N, Abraham LJ, Mercer TR, Park E, Hebert LA, Rovin BH, Birmingham DJ, Chang DM, Chen CJ, McCurdy D, Badsha HM, Thong BY, Chng HH, Arnett FC, Wallace DJ, Yu CY, Hahn BH, Cantor RM, Tsao BP. Association of a common complement receptor 2 haplotype with increased risk of systemic lupus erythematosus. Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):3961-6. Epub 2007 Feb 22. PMID:17360460 doi:0609101104
↑ Thiel J, Kimmig L, Salzer U, Grudzien M, Lebrecht D, Hagena T, Draeger R, Volxen N, Bergbreiter A, Jennings S, Gutenberger S, Aichem A, Illges H, Hannan JP, Kienzler AK, Rizzi M, Eibel H, Peter HH, Warnatz K, Grimbacher B, Rump JA, Schlesier M. Genetic CD21 deficiency is associated with hypogammaglobulinemia. J Allergy Clin Immunol. 2012 Mar;129(3):801-810.e6. doi:, 10.1016/j.jaci.2011.09.027. Epub 2011 Oct 27. PMID:22035880 doi:10.1016/j.jaci.2011.09.027
↑ Barel M, Balbo M, Gauffre A, Frade R. Binding sites of the Epstein-Barr virus and C3d receptor (CR2, CD21) for its three intracellular ligands, the p53 anti-oncoprotein, the p68 calcium binding protein and the nuclear p120 ribonucleoprotein. Mol Immunol. 1995 Apr;32(6):389-97. PMID:7753047
↑ Gilbert HE, Aslam M, Guthridge JM, Holers VM, Perkins SJ. Extended flexible linker structures in the complement chimaeric conjugate CR2-Ig by scattering, analytical ultracentrifugation and constrained modelling: implications for function and therapy. J Mol Biol. 2006 Feb 17;356(2):397-412. Epub 2005 Dec 5. PMID:16375923 doi:10.1016/j.jmb.2005.11.050

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2aty"

@@ Line 3: / Line 3: @@
 <StructureSection load='2aty' size='340' side='right' caption='[[2aty]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2aty]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ATY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ATY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2aty]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ATY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ATY FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1igy|1igy]], [[1ghq|1ghq]], [[1w2r|1w2r]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ighg1, Igh-4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2aty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aty OCA], [http://pdbe.org/2aty PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2aty RCSB], [http://www.ebi.ac.uk/pdbsum/2aty PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2aty ProSAT]</span></td></tr>
 </table>
@@ Line 34: / Line 35: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Aslam, M]]
 [[Category: Gilbert, H E]]

2aty

From Proteopedia

Revision as of 09:30, 12 October 2017

Complement receptor chimaeric conjugate CR2-Ig

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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