1mpv: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| (10 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
< | ==Structure of bhpBR3, the BAFF-binding loop of BR3 embedded in a beta-hairpin peptide== | ||
<StructureSection load='1mpv' size='340' side='right'caption='[[1mpv]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1mpv]] 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=1MPV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MPV FirstGlance]. <br> | |||
</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> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mpv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mpv OCA], [https://pdbe.org/1mpv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mpv RCSB], [https://www.ebi.ac.uk/pdbsum/1mpv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mpv 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 == | |||
The TNF-like ligand BAFF/BLyS is a potent survival factor for B cells. It binds three receptors: TACI, BCMA, and BR3. We show that BR3 signaling promotes processing of the transcription factor NF-kappaB2/p100 to p52. NF-kappaB2/p100 cleavage was abrogated in B cells from A/WySnJ mice possessing a mutant BR3 gene, but not in TACI or BCMA null B cells. Furthermore, wild-type mice injected with BAFF-neutralizing BR3-Fc protein showed reduced basal NF-kappaB2 activation. BR3-Fc treatment of NZB/WF1 mice, which develop a fatal lupus-like syndrome, inhibited NF-kappaB2 processing and attenuated the disease process. Since inhibiting the BR3-BAFF interaction has therapeutic ramifications, the ligand binding interface of BR3 was investigated and found to reside within a 26 residue core domain. When stabilized within a structured beta-hairpin peptide, six of these residues were sufficient to confer binding to BAFF. | The TNF-like ligand BAFF/BLyS is a potent survival factor for B cells. It binds three receptors: TACI, BCMA, and BR3. We show that BR3 signaling promotes processing of the transcription factor NF-kappaB2/p100 to p52. NF-kappaB2/p100 cleavage was abrogated in B cells from A/WySnJ mice possessing a mutant BR3 gene, but not in TACI or BCMA null B cells. Furthermore, wild-type mice injected with BAFF-neutralizing BR3-Fc protein showed reduced basal NF-kappaB2 activation. BR3-Fc treatment of NZB/WF1 mice, which develop a fatal lupus-like syndrome, inhibited NF-kappaB2 processing and attenuated the disease process. Since inhibiting the BR3-BAFF interaction has therapeutic ramifications, the ligand binding interface of BR3 was investigated and found to reside within a 26 residue core domain. When stabilized within a structured beta-hairpin peptide, six of these residues were sufficient to confer binding to BAFF. | ||
BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-kappaB2.,Kayagaki N, Yan M, Seshasayee D, Wang H, Lee W, French DM, Grewal IS, Cochran AG, Gordon NC, Yin J, Starovasnik MA, Dixit VM Immunity. 2002 Oct;17(4):515-24. PMID:12387744<ref>PMID:12387744</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 1mpv" style="background-color:#fffaf0;"></div> | ||
[[Category: Cochran | == References == | ||
[[Category: Dixit | <references/> | ||
[[Category: French | __TOC__ | ||
[[Category: Gordon | </StructureSection> | ||
[[Category: Grewal | [[Category: Homo sapiens]] | ||
[[Category: Kayagaki | [[Category: Large Structures]] | ||
[[Category: Lee | [[Category: Cochran AG]] | ||
[[Category: Seshasayee | [[Category: Dixit VM]] | ||
[[Category: Starovasnik | [[Category: French DM]] | ||
[[Category: Wang | [[Category: Gordon NC]] | ||
[[Category: Yan | [[Category: Grewal IS]] | ||
[[Category: Yin | [[Category: Kayagaki N]] | ||
[[Category: Lee W]] | |||
[[Category: Seshasayee D]] | |||
[[Category: Starovasnik MA]] | |||
[[Category: Wang H]] | |||
[[Category: Yan M]] | |||
[[Category: Yin J]] | |||
Latest revision as of 10:02, 30 October 2024
Structure of bhpBR3, the BAFF-binding loop of BR3 embedded in a beta-hairpin peptideStructure of bhpBR3, the BAFF-binding loop of BR3 embedded in a beta-hairpin peptide
Structural highlights
DiseaseTR13C_HUMAN Defects in TNFRSF13C are the cause of immunodeficiency common variable type 4 (CVID4) [MIM: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.[1] FunctionTR13C_HUMAN B-cell receptor specific for TNFSF13B/TALL1/BAFF/BLyS. Promotes the survival of mature B-cells and the B-cell response.[2] [3] Publication Abstract from PubMedThe TNF-like ligand BAFF/BLyS is a potent survival factor for B cells. It binds three receptors: TACI, BCMA, and BR3. We show that BR3 signaling promotes processing of the transcription factor NF-kappaB2/p100 to p52. NF-kappaB2/p100 cleavage was abrogated in B cells from A/WySnJ mice possessing a mutant BR3 gene, but not in TACI or BCMA null B cells. Furthermore, wild-type mice injected with BAFF-neutralizing BR3-Fc protein showed reduced basal NF-kappaB2 activation. BR3-Fc treatment of NZB/WF1 mice, which develop a fatal lupus-like syndrome, inhibited NF-kappaB2 processing and attenuated the disease process. Since inhibiting the BR3-BAFF interaction has therapeutic ramifications, the ligand binding interface of BR3 was investigated and found to reside within a 26 residue core domain. When stabilized within a structured beta-hairpin peptide, six of these residues were sufficient to confer binding to BAFF. BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-kappaB2.,Kayagaki N, Yan M, Seshasayee D, Wang H, Lee W, French DM, Grewal IS, Cochran AG, Gordon NC, Yin J, Starovasnik MA, Dixit VM Immunity. 2002 Oct;17(4):515-24. PMID:12387744[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||