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3v56

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Revision as of 06:40, 25 December 2014

Re-refinement of PDB entry 1OSG - Complex between BAFF and a BR3 derived peptide presented in a beta-hairpin scaffold - reveals an additonal copy of the peptide.

Structural highlights

3v56 is a 13 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:	,
Related:	1osg
Gene:	TNFSF13B, BAFF, BLYS, TALL1, TNFSF20, ZTNF4, UNQ401/PRO738 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[TN13B_HUMAN] Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. A third B-cell specific BAFF-receptor (BAFFR/BR3) promotes the survival of mature B-cells and the B-cell response.^[1] Isoform 2 seems to inhibit isoform 1 secretion and bioactivity (By similarity).^[2]

Publication Abstract from PubMed

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.

BAFF/BLyS receptor 3 comprises a minimal TNF receptor-like module that encodes a highly focused ligand-binding site.,Gordon NC, Pan B, Hymowitz SG, Yin J, Kelley RF, Cochran AG, Yan M, Dixit VM, Fairbrother WJ, Starovasnik MA Biochemistry. 2003 May 27;42(20):5977-83. PMID:12755599^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, McCabe S, Qiu WR, Kornuc M, Xia XZ, Guo J, Stolina M, Boyle WJ, Sarosi I, Hsu H, Senaldi G, Theill LE. APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity. Nat Immunol. 2000 Sep;1(3):252-6. PMID:10973284 doi:10.1038/79802
↑ Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, McCabe S, Qiu WR, Kornuc M, Xia XZ, Guo J, Stolina M, Boyle WJ, Sarosi I, Hsu H, Senaldi G, Theill LE. APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity. Nat Immunol. 2000 Sep;1(3):252-6. PMID:10973284 doi:10.1038/79802
↑ Gordon NC, Pan B, Hymowitz SG, Yin J, Kelley RF, Cochran AG, Yan M, Dixit VM, Fairbrother WJ, Starovasnik MA. BAFF/BLyS receptor 3 comprises a minimal TNF receptor-like module that encodes a highly focused ligand-binding site. Biochemistry. 2003 May 27;42(20):5977-83. PMID:12755599 doi:10.1021/bi034017g

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3v56"

@@ Line 9: / Line 9: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3v56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v56 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3v56 RCSB], [http://www.ebi.ac.uk/pdbsum/3v56 PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/TN13B_HUMAN TN13B_HUMAN]] Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. A third B-cell specific BAFF-receptor (BAFFR/BR3) promotes the survival of mature B-cells and the B-cell response.<ref>PMID:10973284</ref>   Isoform 2 seems to inhibit isoform 1 secretion and bioactivity (By similarity).<ref>PMID:10973284</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

3v56

From Proteopedia

Revision as of 06:40, 25 December 2014

Re-refinement of PDB entry 1OSG - Complex between BAFF and a BR3 derived peptide presented in a beta-hairpin scaffold - reveals an additonal copy of the peptide.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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