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1osx
From Proteopedia
(Difference between revisions)
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| - | + | ==Solution Structure of the Extracellular Domain of BLyS Receptor 3 (BR3)== | |
| - | + | <StructureSection load='1osx' size='340' side='right' caption='[[1osx]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[1osx]] is a 1 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OSX FirstGlance]. <br> | ||
| + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1mpv|1mpv]], [[1osg|1osg]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFRSF13C OR BAFFR OR BR3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | ||
| + | <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=1osx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1osx RCSB], [http://www.ebi.ac.uk/pdbsum/1osx PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/TR13C_HUMAN TR13C_HUMAN]] Defects in TNFRSF13C are the cause of immunodeficiency common variable type 4 (CVID4) [MIM:[http://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 == | ||
| + | [[http://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. | ||
| - | + | 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
| - | + | ||
| - | + | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Cochran, A G | + | [[Category: Cochran, A G]] |
| - | [[Category: Dixit, V M | + | [[Category: Dixit, V M]] |
| - | [[Category: Fairbrother, W J | + | [[Category: Fairbrother, W J]] |
| - | [[Category: Gordon, N C | + | [[Category: Gordon, N C]] |
| - | [[Category: Hymowitz, S G | + | [[Category: Hymowitz, S G]] |
| - | [[Category: Kelley, R F | + | [[Category: Kelley, R F]] |
| - | [[Category: Pan, B | + | [[Category: Pan, B]] |
| - | [[Category: Starovasnik, M A | + | [[Category: Starovasnik, M A]] |
| - | [[Category: Yan, M | + | [[Category: Yan, M]] |
| - | [[Category: Yin, J P | + | [[Category: Yin, J P]] |
[[Category: Cysteine-rich domain]] | [[Category: Cysteine-rich domain]] | ||
[[Category: Extracellular domain]] | [[Category: Extracellular domain]] | ||
[[Category: Immune system]] | [[Category: Immune system]] | ||
[[Category: Tumor necrosis factor receptor]] | [[Category: Tumor necrosis factor receptor]] | ||
Revision as of 12:57, 18 December 2014
Solution Structure of the Extracellular Domain of BLyS Receptor 3 (BR3)
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