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| | <StructureSection load='3v56' size='340' side='right'caption='[[3v56]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='3v56' size='340' side='right'caption='[[3v56]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3v56]] is a 13 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V56 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V56 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3v56]] is a 13 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V56 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V56 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1osg|1osg]]</div></td></tr>
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| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFSF13B, BAFF, BLYS, TALL1, TNFSF20, ZTNF4, UNQ401/PRO738 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3v56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v56 OCA], [https://pdbe.org/3v56 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v56 RCSB], [https://www.ebi.ac.uk/pdbsum/3v56 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v56 ProSAT]</span></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=3v56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v56 OCA], [https://pdbe.org/3v56 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v56 RCSB], [https://www.ebi.ac.uk/pdbsum/3v56 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v56 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/TN13B_HUMAN TN13B_HUMAN]] Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. A third B-cell specific BAFF-receptor (BAFFR/BR3) promotes the survival of mature B-cells and the B-cell response.<ref>PMID:10973284</ref> Isoform 2 seems to inhibit isoform 1 secretion and bioactivity (By similarity).<ref>PMID:10973284</ref>
| + | [https://www.uniprot.org/uniprot/TN13B_HUMAN TN13B_HUMAN] Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. A third B-cell specific BAFF-receptor (BAFFR/BR3) promotes the survival of mature B-cells and the B-cell response.<ref>PMID:10973284</ref> Isoform 2 seems to inhibit isoform 1 secretion and bioactivity (By similarity).<ref>PMID:10973284</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == 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.
| + | Maximum-likelihood X-ray macromolecular structure refinement in BUSTER has been extended with restraints facilitating the exploitation of structural similarity. The similarity can be between two or more chains within the structure being refined, thus favouring NCS, or to a distinct `target' structure that remains fixed during refinement. The local structural similarity restraints (LSSR) approach considers all distances less than 5.5 A between pairs of atoms in the chain to be restrained. For each, the difference from the distance between the corresponding atoms in the related chain is found. LSSR applies a restraint penalty on each difference. A functional form that reaches a plateau for large differences is used to avoid the restraints distorting parts of the structure that are not similar. Because LSSR are local, there is no need to separate out domains. Some restraint pruning is still necessary, but this has been automated. LSSR have been available to academic users of BUSTER since 2009 with the easy-to-use -autoncs and -target target.pdb options. The use of LSSR is illustrated in the re-refinement of PDB entries 5rnt, where -target enables the correct ligand-binding structure to be found, and 1osg, where -autoncs contributes to the location of an additional copy of the cyclic peptide ligand. |
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| - | 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>
| + | Exploiting structure similarity in refinement: automated NCS and target-structure restraints in BUSTER.,Smart OS, Womack TO, Flensburg C, Keller P, Paciorek W, Sharff A, Vonrhein C, Bricogne G Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):368-80. Epub 2012 Mar 16. PMID:22505257<ref>PMID:22505257</ref> |
| | | | |
| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
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| | ==See Also== | | ==See Also== |
| | *[[Tumor necrosis factor ligand superfamily 3D structures|Tumor necrosis factor ligand superfamily 3D structures]] | | *[[Tumor necrosis factor ligand superfamily 3D structures|Tumor necrosis factor ligand superfamily 3D structures]] |
| - | *[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]] | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bricogne, G]] | + | [[Category: Bricogne G]] |
| - | [[Category: Flensburg, C]] | + | [[Category: Flensburg C]] |
| - | [[Category: Keller, P]] | + | [[Category: Keller P]] |
| - | [[Category: Paciorek, W]] | + | [[Category: Paciorek W]] |
| - | [[Category: Sharff, A]] | + | [[Category: Sharff A]] |
| - | [[Category: Smart, O S]] | + | [[Category: Smart OS]] |
| - | [[Category: Vonrhein, C]] | + | [[Category: Vonrhein C]] |
| - | [[Category: Womack, T O]] | + | [[Category: Womack TO]] |
| - | [[Category: Beta hairpin]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Jelly-roll]]
| + | |
| - | [[Category: Protein-peptide complex]]
| + | |
| Structural highlights
Function
TN13B_HUMAN Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. A third B-cell specific BAFF-receptor (BAFFR/BR3) promotes the survival of mature B-cells and the B-cell response.[1] Isoform 2 seems to inhibit isoform 1 secretion and bioactivity (By similarity).[2]
Publication Abstract from PubMed
Maximum-likelihood X-ray macromolecular structure refinement in BUSTER has been extended with restraints facilitating the exploitation of structural similarity. The similarity can be between two or more chains within the structure being refined, thus favouring NCS, or to a distinct `target' structure that remains fixed during refinement. The local structural similarity restraints (LSSR) approach considers all distances less than 5.5 A between pairs of atoms in the chain to be restrained. For each, the difference from the distance between the corresponding atoms in the related chain is found. LSSR applies a restraint penalty on each difference. A functional form that reaches a plateau for large differences is used to avoid the restraints distorting parts of the structure that are not similar. Because LSSR are local, there is no need to separate out domains. Some restraint pruning is still necessary, but this has been automated. LSSR have been available to academic users of BUSTER since 2009 with the easy-to-use -autoncs and -target target.pdb options. The use of LSSR is illustrated in the re-refinement of PDB entries 5rnt, where -target enables the correct ligand-binding structure to be found, and 1osg, where -autoncs contributes to the location of an additional copy of the cyclic peptide ligand.
Exploiting structure similarity in refinement: automated NCS and target-structure restraints in BUSTER.,Smart OS, Womack TO, Flensburg C, Keller P, Paciorek W, Sharff A, Vonrhein C, Bricogne G Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):368-80. Epub 2012 Mar 16. PMID:22505257[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, McCabe S, Qiu WR, Kornuc M, Xia XZ, Guo J, Stolina M, Boyle WJ, Sarosi I, Hsu H, Senaldi G, Theill LE. APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity. Nat Immunol. 2000 Sep;1(3):252-6. PMID:10973284 doi:10.1038/79802
- ↑ Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, McCabe S, Qiu WR, Kornuc M, Xia XZ, Guo J, Stolina M, Boyle WJ, Sarosi I, Hsu H, Senaldi G, Theill LE. APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity. Nat Immunol. 2000 Sep;1(3):252-6. PMID:10973284 doi:10.1038/79802
- ↑ Smart OS, Womack TO, Flensburg C, Keller P, Paciorek W, Sharff A, Vonrhein C, Bricogne G. Exploiting structure similarity in refinement: automated NCS and target-structure restraints in BUSTER. Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):368-80. Epub 2012 Mar 16. PMID:22505257 doi:10.1107/S0907444911056058
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