6mkz
From Proteopedia
(Difference between revisions)
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<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. 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 [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> |
</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='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> | ||
| + | <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='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'>[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> | ||
</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. | [[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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:30545939</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6mkz" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Lk3 transgenic mice]] | ||
[[Category: Bitra, A]] | [[Category: Bitra, A]] | ||
[[Category: Doukov, T]] | [[Category: Doukov, T]] | ||
Revision as of 08:46, 26 December 2018
Crystal structure of murine 4-1BB/4-1BBL complex
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