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|1p0t, resolution 3.30Å ()|
Crystal Structure of the BAFF-BAFF-R complex (part II)
B-cell activating factor (BAFF) is a key regulator of B-lymphocyte development. Its biological role is mediated by the specific receptors BCMA, TACI and BAFF-R. We have determined the crystal structure of the extracellular domain of BAFF-R bound to BAFF at a resolution of 3.3 A. The cysteine-rich domain (CRD) of the BAFF-R extracellular domain adopts a beta-hairpin structure and binds to the virus-like BAFF cage in a 1:1 molar ratio. The conserved DxL motif of BAFF-R is located on the tip of the beta-turn and is indispensable in the binding of BAFF. The crystal structure shows that a unique dimeric contact occurs between the BAFF-R monomers in the virus-like cage complex. The extracellular domain of TACI contains two CRDs, both of which contain the DxL motif. Modeling of TACI-BAFF complex suggests that both CDRs simultaneously interact with the BAFF dimer in the virus-like cage.
Crystal structure of the BAFF-BAFF-R complex and its implications for receptor activation., Kim HM, Yu KS, Lee ME, Shin DR, Kim YS, Paik SG, Yoo OJ, Lee H, Lee JO, Nat Struct Biol. 2003 May;10(5):342-8. PMID:12715002
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[TR13C_HUMAN] Defects in TNFRSF13C are the cause of immunodeficiency common variable type 4 (CVID4) [MIM:613494]; also called antibody deficiency due to BAFFR defect. CVID4 is 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.
About this Structure
- Kim HM, Yu KS, Lee ME, Shin DR, Kim YS, Paik SG, Yoo OJ, Lee H, Lee JO. Crystal structure of the BAFF-BAFF-R complex and its implications for receptor activation. Nat Struct Biol. 2003 May;10(5):342-8. PMID:12715002 doi:10.1038/nsb925
- ↑ Warnatz K, Salzer U, Rizzi M, Fischer B, Gutenberger S, Bohm J, Kienzler AK, Pan-Hammarstrom Q, Hammarstrom L, Rakhmanov M, Schlesier M, Grimbacher B, Peter HH, Eibel H. B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13945-50. doi:, 10.1073/pnas.0903543106. Epub 2009 Aug 6. PMID:19666484 doi:10.1073/pnas.0903543106
- ↑ Yan M, Brady JR, Chan B, Lee WP, Hsu B, Harless S, Cancro M, Grewal IS, Dixit VM. Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B cell deficiency. Curr Biol. 2001 Oct 2;11(19):1547-52. PMID:11591325
- ↑ Kayagaki N, Yan M, Seshasayee D, Wang H, Lee W, French DM, Grewal IS, Cochran AG, Gordon NC, Yin J, Starovasnik MA, Dixit VM. BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-kappaB2. Immunity. 2002 Oct;17(4):515-24. PMID:12387744