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[[Image:1osx.gif|left|200px]]


{{Structure
==Solution Structure of the Extracellular Domain of BLyS Receptor 3 (BR3)==
|PDB= 1osx |SIZE=350|CAPTION= <scene name='initialview01'>1osx</scene>
<StructureSection load='1osx' size='340' side='right'caption='[[1osx]]' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND=  
<table><tr><td colspan='2'>[[1osx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OSX FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
|GENE= TNFRSF13C OR BAFFR OR BR3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1osx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osx OCA], [https://pdbe.org/1osx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1osx RCSB], [https://www.ebi.ac.uk/pdbsum/1osx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1osx ProSAT]</span></td></tr>
}}
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TR13C_HUMAN TR13C_HUMAN] Defects in TNFRSF13C are the cause of immunodeficiency common variable type 4 (CVID4) [MIM:[https://omim.org/entry/613494 613494]; also called antibody deficiency due to BAFFR defect. CVID4 is a primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.<ref>PMID:19666484</ref>
== Function ==
[https://www.uniprot.org/uniprot/TR13C_HUMAN TR13C_HUMAN] B-cell receptor specific for TNFSF13B/TALL1/BAFF/BLyS. Promotes the survival of mature B-cells and the B-cell response.<ref>PMID:11591325</ref> <ref>PMID:12387744</ref>
<div style="background-color:#fffaf0;">
== 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.


'''Solution Structure of the Extracellular Domain of BLyS Receptor 3 (BR3)'''
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<ref>PMID:12755599</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1osx" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
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.
*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
 
== References ==
==About this Structure==
<references/>
1OSX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSX OCA].
__TOC__
 
</StructureSection>
==Reference==
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:[http://www.ncbi.nlm.nih.gov/pubmed/12755599 12755599]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Cochran, A G.]]
[[Category: Cochran AG]]
[[Category: Dixit, V M.]]
[[Category: Dixit VM]]
[[Category: Fairbrother, W J.]]
[[Category: Fairbrother WJ]]
[[Category: Gordon, N C.]]
[[Category: Gordon NC]]
[[Category: Hymowitz, S G.]]
[[Category: Hymowitz SG]]
[[Category: Kelley, R F.]]
[[Category: Kelley RF]]
[[Category: Pan, B.]]
[[Category: Pan B]]
[[Category: Starovasnik, M A.]]
[[Category: Starovasnik MA]]
[[Category: Yan, M.]]
[[Category: Yan M]]
[[Category: Yin, J P.]]
[[Category: Yin JP]]
[[Category: cysteine-rich domain]]
[[Category: extracellular domain]]
[[Category: tumor necrosis factor receptor]]
 
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