PDBsum entry: 1osg

Immune system

PDB id: 1osg

Contents

Protein chains

(+ 0 more) 144 a.a. *

(+ 0 more) 12 a.a. *

Metals

_MG ×4

Waters ×20

* Residue conservation analysis

PDB id:

1osg

Name:

Immune system

Title:

Complex between baff and a br3 derived peptide presented in a beta-hairpin scaffold

Structure:

Tumor necrosis factor ligand superfamily member 13b. Chain: a, b, c, d, e, f. Fragment: tnf domain. Synonym: tnf-and apol- related leukocyte expressed ligand 1, tall-1, b lymphocyte stimulator, blys, b cell- activating factor, baff, dendritic cell- derived tnf-like molecule. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: baff. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: this peptide was chemically synthesized.

Biol. unit:

Hexamer (from PQS)

Resolution:

3.00Å R-factor: 0.220 R-free: 0.286

Authors:

N.C.Gordon,B.Pan,S.G.Hymowitz,J.P.Yin,R.F.Kelley, A.G.Cochran,M.Yan,V.M.Dixit,W.J.Fairbrother,M.A.Starovasnik

Key ref:

N.C.Gordon et al. (2003). BAFF/BLyS receptor 3 comprises a minimal TNF receptor-like module that encodes a highly focused ligand-binding site. Biochemistry, 42, 5977-5983. PubMed id: 12755599 DOI: 10.1021/bi034017g

Date:

19-Mar-03 Release date: 27-May-03

Protein chains

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

Seq: 285 a.a.

Struc: 144 a.a.

Protein chain

No UniProt id for this chain

 Gene Ontology (GO) functional annotation 

• Cellular component: membrane (1 term)
• Biological process: immune response (1 term)
• Biochemical function: tumor necrosis factor receptor binding (1 term)

DOI no: 10.1021/bi034017g

Biochemistry 42:5977-5983 (2003)

PubMed id: 12755599

BAFF/BLyS receptor 3 comprises a minimal TNF receptor-like module that encodes a highly focused ligand-binding site.

N.C.Gordon, B.Pan, S.G.Hymowitz, J.Yin, R.F.Kelley, A.G.Cochran, M.Yan, V.M.Dixit, W.J.Fairbrother, M.A.Starovasnik.

ABSTRACT

BAFF/BLyS, a member of the tumor necrosis family (TNF) superfamily of ligands, is a crucial survival factor for B cells. BAFF binds three receptors, TACI, BCMA, and BR3, with signaling through BR3 being essential for promoting B cell function. Typical TNF receptor (TNFR) family members bind their cognate ligands through interactions with two cysteine-rich domains (CRDs). However, the extracellular domain (ECD) of BR3 consists of only a partial CRD, with cysteine spacing distinct from other modules described previously. Herein, we report the solution structure of the BR3 ECD. A core region of only 19 residues adopts a stable structure in solution. The BR3 fold is analogous to the first half of a canonical TNFR CRD but is stabilized by an additional noncanonical disulfide bond. BAFF-binding determinants were identified by shotgun alanine-scanning mutagenesis of the BR3 ECD expressed on phage. Several of the key BAFF-binding residues are presented from a beta-turn that we have shown previously to be sufficient for ligand binding when transferred to a structured beta-hairpin scaffold [Kayagaki, N., Yan, M., Seshasayee, D., Wang, H., Lee, W., French, D. M., Grewal, I. S., Cochran, A. G., Gordon, N. C., Yin, J., Starovasnik, M. A, and Dixit, V. M. (2002) Immunity 10, 515-524]. Outside of the turn, mutagenesis identifies additional hydrophobic contacts that enhance the BAFF-BR3 interaction. The crystal structure of the minimal hairpin peptide, bhpBR3, in complex with BAFF reveals intimate packing of the six-residue BR3 turn into a cavity on the ligand surface. Thus, BR3 binds BAFF through a highly focused interaction site, unprecedented in the TNFR family.