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1osx
From Proteopedia
(New page: 200px<br /> <applet load="1osx" size="450" color="white" frame="true" align="right" spinBox="true" caption="1osx" /> '''Solution Structure of the Extracellular Dom...) |
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'''Solution Structure of the Extracellular Domain of BLyS Receptor 3 (BR3)'''<br /> | '''Solution Structure of the Extracellular Domain of BLyS Receptor 3 (BR3)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BAFF/BLyS, a member of the tumor necrosis family (TNF) superfamily of | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1OSX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1OSX is a [http://en.wikipedia.org/wiki/Single_protein 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]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Cochran, A | + | [[Category: Cochran, A G.]] |
| - | [[Category: Dixit, V | + | [[Category: Dixit, V M.]] |
| - | [[Category: Fairbrother, W | + | [[Category: Fairbrother, W J.]] |
| - | [[Category: Gordon, N | + | [[Category: Gordon, N C.]] |
| - | [[Category: Hymowitz, S | + | [[Category: Hymowitz, S G.]] |
| - | [[Category: Kelley, R | + | [[Category: Kelley, R F.]] |
[[Category: Pan, B.]] | [[Category: Pan, B.]] | ||
| - | [[Category: Starovasnik, M | + | [[Category: Starovasnik, M A.]] |
[[Category: Yan, M.]] | [[Category: Yan, M.]] | ||
| - | [[Category: Yin, J | + | [[Category: Yin, J P.]] |
[[Category: cysteine-rich domain]] | [[Category: cysteine-rich domain]] | ||
[[Category: extracellular domain]] | [[Category: extracellular domain]] | ||
[[Category: tumor necrosis factor receptor]] | [[Category: tumor necrosis factor receptor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:21:13 2008'' |
Revision as of 12:21, 21 February 2008
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Solution Structure of the Extracellular Domain of BLyS Receptor 3 (BR3)
Overview
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.
About this Structure
1OSX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
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:12755599
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