6cpr
From Proteopedia
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<StructureSection load='6cpr' size='340' side='right' caption='[[6cpr]], [[Resolution|resolution]] 2.70Å' scene=''> | <StructureSection load='6cpr' size='340' side='right' caption='[[6cpr]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6cpr]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CPR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CPR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6cpr]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CPR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CPR FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFSF9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TNFRSF9, CD137, ILA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6cpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cpr OCA], [http://pdbe.org/6cpr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cpr RCSB], [http://www.ebi.ac.uk/pdbsum/6cpr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cpr ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6cpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cpr OCA], [http://pdbe.org/6cpr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cpr RCSB], [http://www.ebi.ac.uk/pdbsum/6cpr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cpr ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/TNFL9_HUMAN TNFL9_HUMAN]] Cytokine that binds to TNFRSF9. Induces the proliferation of activated peripheral blood T-cells. May have a role in activation-induced cell death (AICD). May play a role in cognate interactions between T-cells and B-cells/macrophages. [[http://www.uniprot.org/uniprot/TNR9_HUMAN TNR9_HUMAN]] Receptor for TNFSF9/4-1BBL. Possibly active during T cell activation. | [[http://www.uniprot.org/uniprot/TNFL9_HUMAN TNFL9_HUMAN]] Cytokine that binds to TNFRSF9. Induces the proliferation of activated peripheral blood T-cells. May have a role in activation-induced cell death (AICD). May play a role in cognate interactions between T-cells and B-cells/macrophages. [[http://www.uniprot.org/uniprot/TNR9_HUMAN TNR9_HUMAN]] Receptor for TNFSF9/4-1BBL. Possibly active during T cell activation. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Human (h)4-1BB (TNFRSF9 or CD137) is an inducible tumor necrosis factor receptor (TNFR) super family member that interacts with its cognate ligand h4-1BBL to promote T lymphocyte activation and proliferation. h4-1BB is currently being targeted with agonists in cancer immunotherapy. Here, we determined the crystal structures of unbound h4-1BBL and both wildtype h4-1BB and a dimerization-deficient h-41BB mutant (C121S) in complex with h4-1BBL at resolutions between 2.7 A and 3.2 A. We observed that the structural arrangement of 4-1BBL, both unbound and in the complex, represents the canonical bell shape as seen in other similar TNF proteins and differs from the previously reported three-bladed propeller structure of 4-1BBL. We also found that the binding site for the receptor is at the crevice formed between two protomers of h4-1BBL, but that h4-1BB interacts predominantly with only one ligand protomer. Moreover, h4-1BBL lacked the conserved tyrosine residue in the DE loop that forms canonical interactions between other TNFR family molecules and their ligands, suggesting h4-1BBL engages h4-1BB through a distinct mechanism. Of note, we discovered that h4-1BB forms a disulfide-linked dimer owing to the presence of an additional cysteine residue found in its cysteine-rich domain 4 (CRD4). As a result, h4-1BB dimerization, in addition to trimerization via h4-1BBL binding, could result in cross-linking of individual ligand-receptor complexes to form a 2D network that stimulates strong h4-1BB signaling. This work provides critical insights into the structural and functional properties of both h4-1BB and h4-1BBL and reveals that covalent receptor dimerization amplifies h4-1BB signaling. | ||
| + | |||
| + | Crystal structures of the human 4-1BB receptor bound to its ligand 4-1BBL reveal covalent receptor dimerization as a potential signaling amplifier.,Bitra A, Doukov T, Croft M, Zajonc DM J Biol Chem. 2018 May 2. pii: RA118.003176. doi: 10.1074/jbc.RA118.003176. PMID:29720398<ref>PMID:29720398</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6cpr" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Aruna, B]] | [[Category: Aruna, B]] | ||
[[Category: Zajonc, D M]] | [[Category: Zajonc, D M]] | ||
[[Category: Complex]] | [[Category: Complex]] | ||
[[Category: Cytokine]] | [[Category: Cytokine]] | ||
Revision as of 06:13, 11 July 2018
Crystal structure of 4-1BBL/4-1BB complex in C2 space group
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Categories: Human | Aruna, B | Zajonc, D M | Complex | Cytokine
