1kd7: Difference between revisions

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[[Image:1kd7.jpg|left|200px]]<br /><applet load="1kd7" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1kd7, resolution 2.80&Aring;" />
'''Crystal structure of an extracellular domain fragment of human BAFF'''<br />


==Overview==
==Crystal structure of an extracellular domain fragment of human BAFF==
B cell activating factor (BAFF), a ligand belonging to the tumor necrosis, factor (TNF) family, plays a critical role in regulating survival and, activation of peripheral B cell populations and has been associated with, autoimmune disease. BAFF is known to interact with three receptors, BCMA, TACI and BAFF-R, that have distant similarities with other receptors of, the TNF family. We have determined the crystal structure of the, TNF-homologous domain of BAFF at 2.8 A resolution. The structure reveals, significant differences when compared to other TNF family members, including an unusually long D-E loop that participates in the formation of, a deep, concave and negatively charged region in the putative receptor, binding site. The BAFF structure was further used to generate a homology, model of APRIL, a closely related TNF family ligand that also binds to, BCMA and TACI, but not BAFF-R. Analysis of the putative receptor binding, sites of BAFF and APRIL suggests that differences in the D-E loop, structure and electrostatic surface potentials may be important for, determining binding specificities for BCMA, TACI and BAFF-R.
<StructureSection load='1kd7' size='340' side='right'caption='[[1kd7]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1kd7]] is a 6 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=1KD7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KD7 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</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=1kd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kd7 OCA], [https://pdbe.org/1kd7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kd7 RCSB], [https://www.ebi.ac.uk/pdbsum/1kd7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kd7 ProSAT]</span></td></tr>
</table>
== 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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kd/1kd7_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1kd7 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
B cell activating factor (BAFF), a ligand belonging to the tumor necrosis factor (TNF) family, plays a critical role in regulating survival and activation of peripheral B cell populations and has been associated with autoimmune disease. BAFF is known to interact with three receptors, BCMA, TACI and BAFF-R, that have distant similarities with other receptors of the TNF family. We have determined the crystal structure of the TNF-homologous domain of BAFF at 2.8 A resolution. The structure reveals significant differences when compared to other TNF family members, including an unusually long D-E loop that participates in the formation of a deep, concave and negatively charged region in the putative receptor binding site. The BAFF structure was further used to generate a homology model of APRIL, a closely related TNF family ligand that also binds to BCMA and TACI, but not BAFF-R. Analysis of the putative receptor binding sites of BAFF and APRIL suggests that differences in the D-E loop structure and electrostatic surface potentials may be important for determining binding specificities for BCMA, TACI and BAFF-R.


==About this Structure==
Crystal structure of extracellular human BAFF, a TNF family member that stimulates B lymphocytes.,Karpusas M, Cachero TG, Qian F, Boriack-Sjodin A, Mullen C, Strauch K, Hsu YM, Kalled SL J Mol Biol. 2002 Feb 1;315(5):1145-54. PMID:11827482<ref>PMID:11827482</ref>
1KD7 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=1KD7 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Crystal structure of extracellular human BAFF, a TNF family member that stimulates B lymphocytes., Karpusas M, Cachero TG, Qian F, Boriack-Sjodin A, Mullen C, Strauch K, Hsu YM, Kalled SL, J Mol Biol. 2002 Feb 1;315(5):1145-54. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11827482 11827482]
</div>
<div class="pdbe-citations 1kd7" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Tumor necrosis factor ligand superfamily 3D structures|Tumor necrosis factor ligand superfamily 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Boriack-Sjodin, A.]]
[[Category: Boriack-Sjodin A]]
[[Category: Cachero, T.G.]]
[[Category: Cachero TG]]
[[Category: Hsu, Y-M.]]
[[Category: Hsu Y-M]]
[[Category: Kalled, S.L.]]
[[Category: Kalled SL]]
[[Category: Karpusas, M.]]
[[Category: Karpusas M]]
[[Category: Mullen, C.]]
[[Category: Mullen C]]
[[Category: Qian, F.]]
[[Category: Qian F]]
[[Category: Strauch, K.]]
[[Category: Strauch K]]
[[Category: beta-sheet shandwich]]
[[Category: tnf]]
 
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