The crystal structure of a proliferation-inducing ligand, APRIL

J Mol Biol. 2004 Oct 15;343(2):283-90. doi: 10.1016/j.jmb.2004.08.040.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • B-Cell Activating Factor
  • B-Cell Maturation Antigen
  • Crystallography, X-Ray
  • Humans
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary*
  • Receptors, Tumor Necrosis Factor / chemistry
  • Receptors, Tumor Necrosis Factor / genetics
  • Sequence Alignment
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Tumor Necrosis Factor-alpha / chemistry*
  • Tumor Necrosis Factor-alpha / genetics


  • B-Cell Activating Factor
  • B-Cell Maturation Antigen
  • Membrane Proteins
  • Receptors, Tumor Necrosis Factor
  • TNFRSF17 protein, human
  • TNFSF13 protein, human
  • TNFSF13B protein, human
  • Tnfrsf17 protein, mouse
  • Tnfsf13 protein, mouse
  • Tnfsf13b protein, mouse
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Tumor Necrosis Factor-alpha

Associated data

  • PDB/15UY
  • PDB/1U5X
  • PDB/1U5Z