|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of murine 4-1BB/4-1BBL complex== | | ==Crystal structure of murine 4-1BB/4-1BBL complex== |
| - | <StructureSection load='6mkz' size='340' side='right' caption='[[6mkz]], [[Resolution|resolution]] 2.65Å' scene=''> | + | <StructureSection load='6mkz' size='340' side='right'caption='[[6mkz]], [[Resolution|resolution]] 2.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6mkz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MKZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MKZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6mkz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MKZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MKZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 2.65Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tnfsf9, Cd137l, Cd157l, Ly63l ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Tnfrsf9, Cd137, Ila, Ly63 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=6mkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mkz OCA], [http://pdbe.org/6mkz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mkz RCSB], [http://www.ebi.ac.uk/pdbsum/6mkz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mkz 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=6mkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mkz OCA], [https://pdbe.org/6mkz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mkz RCSB], [https://www.ebi.ac.uk/pdbsum/6mkz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mkz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TNFL9_MOUSE TNFL9_MOUSE]] 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_MOUSE TNR9_MOUSE]] Receptor for TNFSF9/4-1BBL. Possibly active during T cell activation. | + | [https://www.uniprot.org/uniprot/TNFL9_MOUSE TNFL9_MOUSE] 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 19: |
Line 19: |
| | </div> | | </div> |
| | <div class="pdbe-citations 6mkz" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6mkz" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[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: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Bitra, A]] | + | [[Category: Mus musculus]] |
| - | [[Category: Doukov, T]] | + | [[Category: Bitra A]] |
| - | [[Category: Zajonc, D M]] | + | [[Category: Doukov T]] |
| - | [[Category: Signaling protein]] | + | [[Category: Zajonc DM]] |
| - | [[Category: Tnf]]
| + | |
| - | [[Category: Tnfr]]
| + | |
| Structural highlights
Function
TNFL9_MOUSE 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.
Publication Abstract from PubMed
The interaction between the receptor 4-1BB and its ligand 4-1BBL provides co-stimulatory signals for T-cell activation and proliferation. However, differences in the mouse and human molecules might result in differential engagement of this pathway. Here, we report the crystal structure of mouse 4-1BBL and of the mouse 4-1BB/4-1BBL complex, which together provided insights into the molecular mechanism by which m4-1BBL and its cognate receptor recognize each other. Unlike all human or mouse tumor necrosis factor ligands that form non-covalent and mostly trimeric assemblies, the m4-1BBL structure formed a disulfide-linked dimeric assembly. The structure disclosed that certain differences in the amino acid composition along the intramolecular interface, together with two specific residues (Cys-246 and Ser-256) present exclusively in m4-1BBL, are responsible for unique this dimerization. Unexpectedly, upon m4-1BB binding, m4-1BBL undergoes structural changes within each protomer, moreover, the individual m4-1BBL protomers rotate relative to each other, yielding a dimerization interface with more inter-subunit interactions. We also observed that in the m4-1BB/4-1BBL complex, each receptor monomer binds exclusively to a single ligand subunit with contributions of cysteine-rich domain 1 (CRD1), CRD2, and CRD3. Furthermore, structure-guided mutagenesis of the binding interface revealed that novel binding interactions with the GH loop, rather than the DE loop, are energetically critical and define the m4-1BB receptor selectivity for m4-1BBL. A comparison with the human 4-1BB/4-1BBL complex highlighted several differences between the ligand- and receptor-binding interfaces, providing an explanation for the absence of inter-species cross-reactivity between human and mouse 4-1BB and 4-1BBL molecules.
Crystal structure of the m4-1BB/4-1BBL complex reveals an unusual dimeric ligand that undergoes structural changes upon 4-1BB receptor binding.,Bitra A, Doukov T, Destito G, Croft M, Zajonc DM J Biol Chem. 2018 Dec 13. pii: RA118.006297. doi: 10.1074/jbc.RA118.006297. PMID:30545939[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bitra A, Doukov T, Destito G, Croft M, Zajonc DM. Crystal structure of the m4-1BB/4-1BBL complex reveals an unusual dimeric ligand that undergoes structural changes upon 4-1BB receptor binding. J Biol Chem. 2018 Dec 13. pii: RA118.006297. doi: 10.1074/jbc.RA118.006297. PMID:30545939 doi:http://dx.doi.org/10.1074/jbc.RA118.006297
|
