| Structural highlights
2gsx is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 1ghq, 1w2r, 2aty |
| Gene: | CR2, C3DR (Homo sapiens) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
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 type 2 (CR2, CD21) is a cell surface protein that links the innate and adaptive immune response during the activation of B cells. The extracellular portion of CR2 comprises 15 or 16 short complement regulator (SCR) domains, for which the overall arrangement in solution is unknown. This was determined by constrained scattering and ultracentrifugation modelling. The radius of gyration of CR2 SCR 1-15 was determined to be 11.5 nm by both X-ray and neutron scattering, and that of its cross-section was 1.8 nm. The distance distribution function P(r) showed that the overall length of CR2 SCR 1-15 was 38 nm. Sedimentation equilibrium curve fits gave a mean molecular weight of 135,000 (+/- 13,000) Da, in agreement with a fully glycosylated structure. Velocity experiments using the g*(s) derivative method gave a sedimentation coefficient of 4.2 (+/- 0.1) S. In order to construct a model of CR2 SCR 1-15 for constrained fitting, homology models for the 15 SCR domains were combined with randomised linker peptides generated by molecular dynamics simulations. Using an automated procedure, the analysis of 15,000 possible CR2 SCR 1-15 models showed that only those models in which the 15 SCR domains were flexible but partially folded back accounted for the scattering and sedimentation data. The best-fit CR2 models provided a visual explanation for the versatile interaction of CR2 with four ligands C3d, CD23, gp350 and IFN-alpha. The flexible location of CR2 SCR 1-2 is likely to facilitate interactions of C3d-antigen complexes with the B cell receptor.
The 15 SCR flexible extracellular domains of human complement receptor type 2 can mediate multiple ligand and antigen interactions.,Gilbert HE, Asokan R, Holers VM, Perkins SJ J Mol Biol. 2006 Oct 6;362(5):1132-47. Epub 2006 Aug 9. PMID:16950392[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, Asokan R, Holers VM, Perkins SJ. The 15 SCR flexible extracellular domains of human complement receptor type 2 can mediate multiple ligand and antigen interactions. J Mol Biol. 2006 Oct 6;362(5):1132-47. Epub 2006 Aug 9. PMID:16950392 doi:10.1016/j.jmb.2006.08.012
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