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Cytokine PDB id
1kxg
Jmol
Contents
Protein chains
(+ 0 more) 144 a.a. *
Ligands
CIT ×2
DIO ×20
Metals
_MG ×7
Waters ×462
* Residue conservation analysis
PDB id:
1kxg
Name: Cytokine
Title: The 2.0 ang resolution structure of blys, b lymphocyte stimulator.
Structure: B lymphocyte stimulator. Chain: a, b, c, d, e, f. Fragment: soluble portion (residues 134-285). Synonym: blys, tumor necrosis factor ligand superfamily member 13b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.
Biol. unit: Trimer (from PQS)
Resolution:
2.00Å     R-factor:   0.189     R-free:   0.209
Authors: D.A.Oren,Y.Li,Y.Volovik,T.S.Morris,C.Dharia,K.Das, O.Galperina,R.Gentz,E.Arnold
Key ref:
D.A.Oren et al. (2002). Structural basis of BLyS receptor recognition. Nat Struct Biol, 9, 288-292. PubMed id: 11862220 DOI: 10.1038/nsb769
Date:
31-Jan-02     Release date:   20-Mar-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9Y275  (TN13B_HUMAN) -  Tumor necrosis factor ligand superfamily member 13B
Seq:
Struc: 		285 a.a.
144 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     immune response   1 term 
  Biochemical function     tumor necrosis factor receptor binding     1 term  

 

 
DOI no: 10.1038/nsb769 Nat Struct Biol 9:288-292 (2002)
PubMed id: 11862220  
 
 
Structural basis of BLyS receptor recognition.
D.A.Oren, Y.Li, Y.Volovik, T.S.Morris, C.Dharia, K.Das, O.Galperina, R.Gentz, E.Arnold.
 
  ABSTRACT  
 
B lymphocyte stimulator (BLyS), a member of the tumor necrosis factor (TNF) superfamily, is a cytokine that induces B-cell proliferation and immunoglobulin secretion. We have determined the three-dimensional structure of BLyS to 2.0 A resolution and identified receptor recognition segments using limited proteolysis coupled with mass spectrometry. Similar to other structurally determined TNF-like ligands, the BLyS monomer is a beta-sandwich and oligomerizes to form a homotrimer. The receptor-binding region in BLyS is a deeper, more pronounced groove than in other cytokines. The conserved elements on the 'floor' of this groove allow for cytokine recognition of several structurally related receptors, whereas variations on the 'walls' and outer rims of the groove confer receptor specificity.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. BLyS structure. Ribbon diagrams (using RIBBONS39) of a, BLyS (left) and TNF- (right) are shown down the three-fold axis of the trimer, and b, rotated 90° about the horizontal viewing axis. Strands of two of the three monomers are color coded as in Fig. 1. Gln 234 is green; Asn 243, yellow; Mg2+, brown; and waters, red. The metals have a coordination sphere of six, and metal -ligand distances range between 2.4 Å and 2.8 Å. The BLyS trimer has a wider and shorter shape than that of TNF- . c, SIGMAA^35-weighted electron density map using 2mF[o] - F[c] coefficients and contoured at 1 . Shown is the region of the three-fold axis (vertical in the viewing plane), highlighting the high quality of the refined electron density, the geometry of the metal coordination and the presence of a dioxane molecule. The electron density associated with the hydrated metals is colored in magenta for clarity. 		Figure 4.
Figure 4. Putative BLyS -receptor interactions. a, Superimposed TNF-R (red ribbon) docked on BLyS surface representation, color-coded by monomer as in Fig. 3, with groove residues in green. The orientation on the left is as in Fig. 3. The middle image is the same but rotated 90° about the horizontal viewing axis. On the right, groove residues in common between BLyS and APRIL are colored red, implicating contacts with TACI and BCMA receptors. The residues forming the groove from adjacent monomers are Gln 148, Ile 150, Ala 151, Asp 152, Ser 153, Glu 154, Leu 169, Leu 170, Phe 172, Leu 200, Thr 202, Ile 270, Ser 271, Leu 272, Asp 273, Glu 274, Asp 275 and Phe 278 from one monomer, and Thr 190, Tyr 192, Ala 207, Gly 209, His 210, Leu 211, Gln 213, Arg 214, Lys 216, His 218, Phe 220, Asp 222, Glu 223, Leu 224, Leu 226, Val 227, Thr 228, Leu 229, Phe 230, Arg 231, Ile 233, Ala 251, Lys 252, Leu 253, Glu 254 and Asp 257 from another monomer. Those in common with APRIL are underlined. b, PAWS coverage analysis, mapping fragments found in SELDI binding assays of TACI and BMCA to areas in the BLyS sequence. Red boxes highlight areas of strongest coverage. Binding-site mapping was done by in situ trypsin digestion of the captured ligand, followed by mass spectrometric identification of retained fragments. Arrows mark BLyS -strands.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2002, 9, 288-292) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19404965 C.Rochas, S.Hillion, A.Saraux, R.A.Mageed, P.Youinou, C.Jamin, and V.Devauchelle (2009).
Transmembrane BAFF from rheumatoid synoviocytes requires interleukin-6 to induce the expression of recombination-activating gene in B lymphocytes.
  Arthritis Rheum, 60, 1261-1271.  
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.  
18155417 A.Binard, L.Le Pottier, A.Saraux, V.Devauchelle-Pensec, J.O.Pers, and P.Youinou (2008).
Does the BAFF dysregulation play a major role in the pathogenesis of systemic lupus erythematosus?
  J Autoimmun, 30, 63-67.  
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.  
16604261 Q.Shen, S.X.Li, F.H.Fu, Q.S.Yuan, and Y.Gong (2006).
Two observed regions in B lymphocyte stimulator important for its biological activity.
  Acta Biochim Biophys Sin (Shanghai), 38, 227-232.  
15653362 J.G.Stroh, P.Loulakis, A.J.Lanzetti, and J.Xie (2005).
LC-mass spectrometry analysis of N- and C-terminal boundary sequences of polypeptide fragments by limited proteolysis.
  J Am Soc Mass Spectrom, 16, 38-45.  
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
16276047 T.Matsushita, and S.Sato (2005).
[The role of BAFF in autoimmune diseases]
  Nihon Rinsho Meneki Gakkai Kaishi, 28, 333-342.  
14707116 B.P.O'Connor, V.S.Raman, L.D.Erickson, W.J.Cook, L.K.Weaver, C.Ahonen, L.L.Lin, G.T.Mantchev, R.J.Bram, and R.J.Noelle (2004).
BCMA is essential for the survival of long-lived bone marrow plasma cells.
  J Exp Med, 199, 91-98.  
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.  
14625891 N.Tang, P.Tornatore, and S.R.Weinberger (2004).
Current developments in SELDI affinity technology.
  Mass Spectrom Rev, 23, 34-44.  
15161425 W.Stohl (2004).
Targeting B lymphocyte stimulator in systemic lupus erythematosus and other autoimmune rheumatic disorders.
  Expert Opin Ther Targets, 8, 177-189.  
12867412 A.L.Gavin, D.Aït-Azzouzene, C.F.Ware, and D.Nemazee (2003).
DeltaBAFF, an alternate splice isoform that regulates receptor binding and biopresentation of the B cell survival cytokine, BAFF.
  J Biol Chem, 278, 38220-38228.  
  12787568 F.Mackay, and C.Ambrose (2003).
The TNF family members BAFF and APRIL: the growing complexity.
  Cytokine Growth Factor Rev, 14, 311-324.  
12427767 F.Mackay, P.Schneider, P.Rennert, and J.Browning (2003).
BAFF AND APRIL: a tutorial on B cell survival.
  Annu Rev Immunol, 21, 231-264.  
12715002 H.M.Kim, K.S.Yu, M.E.Lee, D.R.Shin, Y.S.Kim, S.G.Paik, O.J.Yoo, H.Lee, and J.O.Lee (2003).
Crystal structure of the BAFF-BAFF-R complex and its implications for receptor activation.
  Nat Struct Biol, 10, 342-348.
PDB codes: 1otz 1p0t
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.  
14732928 R.L.Rich, and D.G.Myszka (2003).
A survey of the year 2002 commercial optical biosensor literature.
  J Mol Recognit, 16, 351-382.  
  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 code: 1rj8
12556207 S.L.Kalled, C.Ambrose, and Y.M.Hsu (2003).
BAFF: B cell survival factor and emerging therapeutic target for autoimmune disorders.
  Expert Opin Ther Targets, 7, 115-123.  
12721620 Y.Liu, X.Hong, J.Kappler, L.Jiang, R.Zhang, L.Xu, C.H.Pan, W.E.Martin, R.C.Murphy, H.B.Shu, S.Dai, and G.Zhang (2003).
Ligand-receptor binding revealed by the TNF family member TALL-1.
  Nature, 423, 49-56.
PDB codes: 1oqd 1oqe
12666149 C.E.Forde, and S.L.McCutchen-Maloney (2002).
Characterization of transcription factors by mass spectrometry and the role of SELDI-MS.
  Mass Spectrom Rev, 21, 419-439.  
12192248 W.Stohl (2002).
Systemic lupus erythematosus: a blissless disease of too much BLyS (B lymphocyte stimulator) protein.
  Curr Opin Rheumatol, 14, 522-528.  
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 codes are shown on the right.