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PDBsum entry 1p0t

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protein Protein-protein interface(s) links
Protein binding PDB id
1p0t
Jmol
Contents
Protein chains
(+ 54 more) 25 a.a.
PDB id:
1p0t
Name: Protein binding
Title: Crystal structure of the baff-baff-r complex (part ii)
Structure: Tumor necrosis factor receptor superfamily member 13c. Chain: a, b, c, d, e, f, g, h, i, j, k, l, m, n, o, p, q, r, s, t, u, v, w, x, y, z, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, a, b, c, d, e, f, g, h, i, j, k, l, m, n, o, p, q, r, s, t, u, v, w, x. Fragment: residues 1-63. Synonym: baff-r, b cell-activating factor receptor. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: hi5.
Resolution:
3.30Å     R-factor:   0.218     R-free:   0.226
Authors: H.M.Kim,K.S.Yu,M.E.Lee,D.R.Shin,Y.S.Kim,S.G.Paik,O.J.Yoo, H.Lee,J.-O.Lee
Key ref:
H.M.Kim et al. (2003). Crystal structure of the BAFF-BAFF-R complex and its implications for receptor activation. Nat Struct Biol, 10, 342-348. PubMed id: 12715002 DOI: 10.1038/nsb925
Date:
10-Apr-03     Release date:   06-May-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q96RJ3  (TR13C_HUMAN) -  Tumor necrosis factor receptor superfamily member 13C
Seq:
Struc:
184 a.a.
25 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1038/nsb925 Nat Struct Biol 10:342-348 (2003)
PubMed id: 12715002  
 
 
Crystal structure of the BAFF-BAFF-R complex and its implications for receptor activation.
H.M.Kim, K.S.Yu, M.E.Lee, D.R.Shin, Y.S.Kim, S.G.Paik, O.J.Yoo, H.Lee, J.O.Lee.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Structure of the BAFF-R extracellular domains bound to the virus-like BAFF cage. a, Stereo view of a [A]-weighted, simulated annealing, F[o] - F[c] omit electron density map (1.5 ). The residues located within 5 from Leu28 of BAFF-R were omitted for the map calculation. b,c, Overall structure of the BAFF -BAFF-R complex looking down the five-fold axis (b) and looking down the three-fold axis (c). The molecular surface of the BAFF cage is drawn in gray, and the dimeric pairs of BAFF-R are drawn in blue and red. d, A close-up view of the BAFF and BAFF-R complex. Viewing orientation is similar to that of c. The subunits of the BAFF-R dimers are shown in blue and red and are enclosed in boxes. The BAFF dimers are colored green, yellow or gray.
Figure 5.
Figure 5. Characterization of the BAFF and TACI interaction. a, Binding of TACI CRD1 (residues 14 -69) and CRD2 (residues 67 -111) to BAFF. The conserved Asp and Leu residues of the DxL motifs are mutated to alanines in the mutants (M). The TACI FL is the extracellular domain (residues 1 -156) of the full-length TACI. After the binding assay, the resulting duplicate SDS-PAGE gels were visualized either by Coomassie staining or by immunoblot analysis using a polyclonal antibody specific to BAFF (Upstate Biotech) (see Methods). b, Interaction of the TACI CRDs with BAFF. C1M contains mutations of Asp41 and Leu43 of the first DxL motif to alanines. C2M contains mutations of Asp80 and Leu82 of the second DxL motif to alanines. C1,2M contains simultaneous double alanine mutations of both DxL motifs of TACI FL. The resulting duplicate SDS-PAGE gels were visualized as in a. c, CRD1 and CRD2 share the same binding site as BAFF. BAFF DE has a deletion of the DE loop. The R265A BAFF DE mutant has a mutation of Arg265 to alanine and a deletion of the DE loop. C1M, C2M and C1,2M are TACI mutants, as described in b. The resulting duplicate SDS-PAGE gels were visualized as in a. The flexible His[6] tag of the BAFF DE mutant was partially digested during purification and runs as a diffuse band in the SDS-PAGE gel. d, Model of the TACI extracellular domain bound to BAFF. The TACI extracellular domain (residues 32 -104) is shown in a broken black line. Negatively and positively charged surfaces of BAFF are colored red and blue, respectively. The N and C termini of the TACI extracellular domain are indicated. Viewing orientation is similar to that of Fig. 3b. A1 and C2 modules of CRDs are indicated. The structures of the A1 modules were built with that of BAFF-R CRD as a template. The structures of the C2 modules and the angles between the A1 and C2 modules were adopted from the structure of TNFR1 CRD4 for model building. The molecular modeling was carried out using WHATIF^43.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2003, 10, 342-348) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19241374 F.He, W.Dang, K.Saito, S.Watanabe, N.Kobayashi, P.Güntert, T.Kigawa, A.Tanaka, Y.Muto, and S.Yokoyama (2009).
Solution structure of the cysteine-rich domain in Fn14, a member of the tumor necrosis factor receptor superfamily.
  Protein Sci, 18, 650-656.
PDB code: 2rpj
19557629 G.Ferrer, K.Hodgson, E.Montserrat, and C.Moreno (2009).
B cell activator factor and a proliferation-inducing ligand at the cross-road of chronic lymphocytic leukemia and autoimmunity.
  Leuk Lymphoma, 50, 1075-1082.  
17942754 C.Bossen, T.G.Cachero, A.Tardivel, K.Ingold, L.Willen, M.Dobles, M.L.Scott, A.Maquelin, E.Belnoue, C.A.Siegrist, S.Chevrier, H.Acha-Orbea, H.Leung, F.Mackay, J.Tschopp, and P.Schneider (2008).
TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts.
  Blood, 111, 1004-1012.  
18784835 M.R.Schmidt, M.C.Appel, L.J.Giassi, D.L.Greiner, L.D.Shultz, and R.T.Woodland (2008).
Human BLyS facilitates engraftment of human PBL derived B cells in immunodeficient mice.
  PLoS ONE, 3, e3192.  
17492055 L.Garibyan, A.A.Lobito, R.M.Siegel, M.E.Call, K.W.Wucherpfennig, and R.S.Geha (2007).
Dominant-negative effect of the heterozygous C104R TACI mutation in common variable immunodeficiency (CVID).
  J Clin Invest, 117, 1550-1557.  
16914324 C.Bossen, and P.Schneider (2006).
BAFF, APRIL and their receptors: structure, function and signaling.
  Semin Immunol, 18, 263-275.  
16557636 L.L.Kiessling, J.E.Gestwicki, and L.E.Strong (2006).
Synthetic multivalent ligands as probes of signal transduction.
  Angew Chem Int Ed Engl, 45, 2348-2368.  
16474316 S.R.Dillon, J.A.Gross, S.M.Ansell, and A.J.Novak (2006).
An APRIL to remember: novel TNF ligands as therapeutic targets.
  Nat Rev Drug Discov, 5, 235-246.  
15944757 M.Y.Liu, W.Han, Y.L.Ding, T.H.Zhou, R.Y.Tian, S.L.Yang, H.Liu, and Y.Gong (2005).
Generation and characterization of C305, a murine neutralizing scFv antibody that can inhibit BLyS binding to its receptor BCMA.
  Acta Biochim Biophys Sin (Shanghai), 37, 415-420.  
15802951 N.K.Krishna (2005).
Identification of structural domains involved in astrovirus capsid biology.
  Viral Immunol, 18, 17-26.  
15886118 P.Schneider (2005).
The role of APRIL and BAFF in lymphocyte activation.
  Curr Opin Immunol, 17, 282-289.  
15542592 S.G.Hymowitz, D.R.Patel, H.J.Wallweber, S.Runyon, M.Yan, J.Yin, S.K.Shriver, N.C.Gordon, B.Pan, N.J.Skelton, R.F.Kelley, and M.A.Starovasnik (2005).
Structures of APRIL-receptor complexes: like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding.
  J Biol Chem, 280, 7218-7227.
PDB codes: 1xu1 1xu2 1xut
14764606 D.R.Patel, H.J.Wallweber, J.Yin, S.K.Shriver, S.A.Marsters, N.C.Gordon, M.A.Starovasnik, and R.F.Kelley (2004).
Engineering an APRIL-specific B cell maturation antigen.
  J Biol Chem, 279, 16727-16735.  
15093829 G.Zhang (2004).
Tumor necrosis factor family ligand-receptor binding.
  Curr Opin Struct Biol, 14, 154-160.  
15546397 M.P.Cancro (2004).
The BLyS family of ligands and receptors: an archetype for niche-specific homeostatic regulation.
  Immunol Rev, 202, 237-249.  
15084273 R.Lesley, Y.Xu, S.L.Kalled, D.M.Hess, S.R.Schwab, H.B.Shu, and J.G.Cyster (2004).
Reduced competitiveness of autoantigen-engaged B cells due to increased dependence on BAFF.
  Immunity, 20, 441-453.  
15161425 W.Stohl (2004).
Targeting B lymphocyte stimulator in systemic lupus erythematosus and other autoimmune rheumatic disorders.
  Expert Opin Ther Targets, 8, 177-189.  
12796483 M.Pelletier, J.S.Thompson, F.Qian, S.A.Bixler, D.Gong, T.Cachero, K.Gilbride, E.Day, M.Zafari, C.Benjamin, L.Gorelik, A.Whitty, S.L.Kalled, C.Ambrose, and Y.M.Hsu (2003).
Comparison of soluble decoy IgG fusion proteins of BAFF-R and BCMA as antagonists for BAFF.
  J Biol Chem, 278, 33127-33133.  
14656435 S.G.Hymowitz, D.M.Compaan, M.Yan, H.J.Wallweber, V.M.Dixit, M.A.Starovasnik, and A.M.de Vos (2003).
The crystal structures of EDA-A1 and EDA-A2: splice variants with distinct receptor specificity.
  Structure, 11, 1513-1520.
PDB codes: 1rj7 1rj8
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.