PDBsum entry 4zch

Cytokine

PDB id: 4zch

Contents

Protein chains

422 a.a.

Ligands

144

Waters ×339

PDB id:

4zch

Name:

Cytokine

Title:

Single-chain human april-baff-baff heterotrimer

Structure:

Tumor necrosis factor ligand superfamily member 13,tumor necrosis factor ligand superfamily member 13b,tumor necrosis factor ligand superfamily member 13b. Chain: a, b. Synonym: a proliferation-inducing ligand,april,tnf- and apol-related leukocyte expressed ligand 2,tall-2,tnf-related death ligand 1,trdl- 1,b lymphocyte stimulator,blys,b-cell-activating factor,baff, dendritic cell-derived tnf-like molecule,tnf- and apol-related leukocyte expressed ligand 1,tall-1,b lymphocyte stimulator,blys,b-

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tnfsf13, april, tall2, ztnf2, unq383/pro715, tnfsf13b, baff, blys, tall1, tnfsf20, ztnf4, unq401/pro738. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293

Resolution:

2.43Å R-factor: 0.179 R-free: 0.234

Authors:

A.Lammens,X.Jiang,K.Maskos,P.Schneider

Key ref:

S.Schuepbach-Mallepell et al. (2015). Stoichiometry of Heteromeric BAFF and APRIL Cytokines Dictates Their Receptor Binding and Signaling Properties. J Biol Chem, 290, 16330-16342. PubMed id: 25953898 DOI: 10.1074/jbc.M115.661405

Date:

16-Apr-15 Release date: 13-May-15

Protein chains

O75888  (TNF13_HUMAN) -  Tumor necrosis factor ligand superfamily member 13 from Homo sapiens

Seq: 250 a.a.

Struc: 422 a.a.*

Protein chains

Q9Y275  (TN13B_HUMAN) -  Tumor necrosis factor ligand superfamily member 13B from Homo sapiens

Seq: 285 a.a.

Struc: 422 a.a.*

* PDB and UniProt seqs differ at 125 residue positions (black crosses)

DOI no: 10.1074/jbc.M115.661405

J Biol Chem 290:16330-16342 (2015)

PubMed id: 25953898

Stoichiometry of Heteromeric BAFF and APRIL Cytokines Dictates Their Receptor Binding and Signaling Properties.

S.Schuepbach-Mallepell, D.Das, L.Willen, M.Vigolo, A.Tardivel, L.Lebon, C.Kowalczyk-Quintas, J.Nys, C.Smulski, T.S.Zheng, K.Maskos, A.Lammens, X.Jiang, H.Hess, S.L.Tan, P.Schneider.

ABSTRACT

The closely related TNF family ligands B cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) serve in the generation and maintenance of mature B-lymphocytes. Both BAFF and APRIL assemble as homotrimers that bind and activate several receptors that they partially share. However, heteromers of BAFF and APRIL that occur in patients with autoimmune diseases are incompletely characterized. The N and C termini of adjacent BAFF or APRIL monomers are spatially close and can be linked to create single-chain homo- or hetero-ligands of defined stoichiometry. Similar to APRIL, heteromers consisting of one BAFF and two APRILs (BAA) bind to the receptors B cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI) but not to the BAFF receptor (BAFFR). Heteromers consisting of one APRIL and two BAFF (ABB) bind to TACI and BCMA and weakly to BAFFR in accordance with the analysis of the receptor interaction sites in the crystallographic structure of ABB. Receptor binding correlated with activity in reporter cell line assays specific for BAFFR, TACI, or BCMA. Single-chain BAFF (BBB) and to a lesser extent single-chain ABB, but not APRIL or single-chain BAA, rescued BAFFR-dependent B cell maturation in BAFF-deficient mice. In conclusion, BAFF-APRIL heteromers of different stoichiometries have distinct receptor-binding properties and activities. Based on the observation that heteromers are less active than BAFF, we speculate that their physiological role might be to down-regulate BAFF activity.