1mpv
From Proteopedia
(New page: 200px<br /> <applet load="1mpv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mpv" /> '''Structure of bhpBR3, the BAFF-binding loop ...) |
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| - | [[Image:1mpv.gif|left|200px]]<br /> | + | [[Image:1mpv.gif|left|200px]]<br /><applet load="1mpv" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1mpv" size=" | + | |
caption="1mpv" /> | caption="1mpv" /> | ||
'''Structure of bhpBR3, the BAFF-binding loop of BR3 embedded in a beta-hairpin peptide'''<br /> | '''Structure of bhpBR3, the BAFF-binding loop of BR3 embedded in a beta-hairpin peptide'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The TNF-like ligand BAFF/BLyS is a potent survival factor for B cells. It | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1MPV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with ACE and NH2 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1MPV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=ACE:'>ACE</scene> and <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MPV OCA]. |
==Reference== | ==Reference== | ||
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12387744 12387744] | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12387744 12387744] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Cochran, A | + | [[Category: Cochran, A G.]] |
| - | [[Category: Dixit, V | + | [[Category: Dixit, V M.]] |
| - | [[Category: French, D | + | [[Category: French, D M.]] |
| - | [[Category: Gordon, N | + | [[Category: Gordon, N C.]] |
| - | [[Category: Grewal, I | + | [[Category: Grewal, I S.]] |
[[Category: Kayagaki, N.]] | [[Category: Kayagaki, N.]] | ||
[[Category: Lee, W.]] | [[Category: Lee, W.]] | ||
[[Category: Seshasayee, D.]] | [[Category: Seshasayee, D.]] | ||
| - | [[Category: Starovasnik, M | + | [[Category: Starovasnik, M A.]] |
[[Category: Wang, H.]] | [[Category: Wang, H.]] | ||
[[Category: Yan, M.]] | [[Category: Yan, M.]] | ||
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[[Category: beta-hairpin]] | [[Category: beta-hairpin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:57:46 2008'' |
Revision as of 11:57, 21 February 2008
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Structure of bhpBR3, the BAFF-binding loop of BR3 embedded in a beta-hairpin peptide
Overview
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.
About this Structure
1MPV is a Single protein structure of sequence from [1] with and as ligands. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 13:57:46 2008
Categories: Single protein | Cochran, A G. | Dixit, V M. | French, D M. | Gordon, N C. | Grewal, I S. | Kayagaki, N. | Lee, W. | Seshasayee, D. | Starovasnik, M A. | Wang, H. | Yan, M. | Yin, J. | ACE | NH2 | Beta-hairpin
