PDBsum entry 1u5x

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Cytokine, hormone/growth factor PDB id
Protein chain
130 a.a. *
Waters ×43
* Residue conservation analysis
PDB id:
Name: Cytokine, hormone/growth factor
Title: Crystal structure of murine april at ph 5.0
Structure: Tumor necrosis factor ligand superfamily member 1 chain: a. Fragment: tnf domain of murine april. Synonym: a proliferation- inducing ligand, april. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: tnfsf13, april. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Trimer (from PDB file)
1.80Å     R-factor:   0.218     R-free:   0.256
Authors: H.J.Wallweber,D.M.Compaan,M.A.Starovasnik,S.G.Hymowitz
Key ref:
H.J.Wallweber et al. (2004). The crystal structure of a proliferation-inducing ligand, APRIL. J Mol Biol, 343, 283-290. PubMed id: 15451660 DOI: 10.1016/j.jmb.2004.08.040
28-Jul-04     Release date:   12-Oct-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9D777  (TNF13_MOUSE) -  Tumor necrosis factor ligand superfamily member 13
241 a.a.
130 a.a.
Key:    PfamA 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: 10.1016/j.jmb.2004.08.040 J Mol Biol 343:283-290 (2004)
PubMed id: 15451660  
The crystal structure of a proliferation-inducing ligand, APRIL.
H.J.Wallweber, D.M.Compaan, M.A.Starovasnik, S.G.Hymowitz.
A proliferation-inducing ligand (APRIL) is a TNF-like cytokine that stimulates tumor cell growth. Within the TNF ligand superfamily, APRIL is most similar to B-cell activation factor (BAFF) with which it shares 30% sequence identity. APRIL binds the receptors B-cell maturation antigen (BCMA) and TACI with high affinity; both of these receptors have also been shown to bind BAFF, although BCMA has significantly higher affinity for APRIL than BAFF. Determination of the crystal structure of APRIL from three crystallization conditions at resolutions of 1.8-2.4A over a pH range from 5.0 to 8.5 reveals a compact trimeric ligand with a backbone fold very similar to that of BAFF (1.1A RMSD over 122 structurally equivalent Calpha atoms), with the exception of differences in the AA' and DE loop regions. Whereas BAFF has been shown to form 20-trimer assemblies under certain conditions, the molecular determinants required for BAFF-like assemblies are absent in the APRIL structure. No crystal packing suggestive of the formation of higher-order assemblies is seen in any of the crystal forms nor does the structure vary significantly between pH 5.0 and 8.5. Modeling of the APRIL-BCMA complex shows the resulting interface is in agreement with mutagenesis data.
  Selected figure(s)  
Figure 1.
Figure 1. The crystal structure of APRIL. (a) Cartoon of the APRIL trimer from the C2 crystal form. The A chain is colored in gradations from blue (N terminus) to red (C terminus) with strands labeled. The other two protomers are colored white. (b) Superposition of a ribbon carbon-a trace of the five independent APRIL protomers. The pH 5.0 (space group I23) protomer is colored red, the pH 8.5 (space group I23) protomer is colored blue, and chains A, B, and D from the pH 8.0 (space group C2) structure are colored white, beige, and grey, respectively. The disulfide connecting the E and F strands is rendered as sticks. Average pairwise rmsd for backbone atoms in the ordered regions is 0.61±0.08 Å. All Figures were made with PyMol.31
Figure 2.
Figure 2. The molecular surface of APRIL. (a) Electrostatic surface potential of APRIL (C2 crystal form grown at pH 8.0) shown at -5 kT (red) to 5 kT (blue). For the calculation and display of the electrostatic surface potential, disordered charged side-chains (Lys119 in chain A, Arg180 and Arg222 in chain B) were modeled using standard rotamers. Charged residues expected to interact with receptor are labeled. The receptor-binding site is circled. An arrow indicates the position of the 3-fold axis of the trimer. (b) The predicted receptor-binding site is identical in human and murine APRIL. Residues that differ between human and murine APRIL are colored green. Residues corresponding to BAFF residues that bury >50% of their accessible surface area upon binding BCMA18 are colored red. Asp123, which is predicted to interact with BCMA is also colored red and labeled. Residues in the receptor binding site which differ between APRIL and BAFF are labeled with the APRIL residue preceding the number and the BAFF residue following. The expected receptor binding area is outlined in black. The predicted N-glycosylation site conserved in murine and human APRIL is colored purple. A purple asterisk marks the location of the additional predicted N-glycosylation site in human APRIL. An arrow indicates the position of the 3-fold axis of the trimer.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 343, 283-290) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19034695 J.F.Treml, Y.Hao, J.E.Stadanlick, and M.P.Cancro (2009).
The BLyS family: toward a molecular understanding of B cell homeostasis.
  Cell Biochem Biophys, 53, 1.  
20477641 S.Ahn, and C.Cunningham-Rundles (2009).
Role of B cells in common variable immune deficiency.
  Expert Rev Clin Immunol, 5, 557-564.  
19466596 W.Ding, S.Ju, S.Jiang, L.Zhu, Y.Wang, and H.Wang (2009).
Reduced APRIL expression induces cellular senescence via a HSPG-dependent pathway.
  Pathol Oncol Res, 15, 693-701.  
17983875 L.Zhang, L.Radigan, U.Salzer, T.W.Behrens, B.Grimbacher, G.Diaz, J.Bussel, and C.Cunningham-Rundles (2007).
Transmembrane activator and calcium-modulating cyclophilin ligand interactor mutations in common variable immunodeficiency: clinical and immunologic outcomes in heterozygotes.
  J Allergy Clin Immunol, 120, 1178-1185.  
17021878 Z.Guan, W.Yao, J.Ye, W.Dan, J.Shen, and S.Zhang (2007).
The construction and characterization of a bifunctional EGFP/sAPRIL fusion protein.
  Appl Microbiol Biotechnol, 73, 1114-1122.  
16905106 D.M.Compaan, and S.G.Hymowitz (2006).
The crystal structure of the costimulatory OX40-OX40L complex.
  Structure, 14, 1321-1330.
PDB codes: 2hev 2hew 2hey
16827889 S.Haiat, C.Billard, C.Quiney, F.Ajchenbaum-Cymbalista, and J.P.Kolb (2006).
Role of BAFF and APRIL in human B-cell chronic lymphocytic leukaemia.
  Immunology, 118, 281-292.  
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.  
15846369 J.Hendriks, L.Planelles, Jong-Odding, G.Hardenberg, S.T.Pals, M.Hahne, M.Spaargaren, and J.P.Medema (2005).
Heparan sulfate proteoglycan binding promotes APRIL-induced tumor cell proliferation.
  Cell Death Differ, 12, 637-648.  
15851487 K.Ingold, A.Zumsteg, A.Tardivel, B.Huard, Q.G.Steiner, T.G.Cachero, F.Qiang, L.Gorelik, S.L.Kalled, H.Acha-Orbea, P.D.Rennert, J.Tschopp, and P.Schneider (2005).
Identification of proteoglycans as the APRIL-specific binding partners.
  J Exp Med, 201, 1375-1383.  
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
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