6mhr: Difference between revisions

Latest revision as of 08:08, 17 October 2024

Structure of the human 4-1BB / Urelumab Fab complex

Structural highlights

6mhr is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
Ligands:	BMA, EPE, FUC, GOL, MLI, NAG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

4-1BB (CD137, TNFRSF9) is an inducible costimulatory receptor expressed on activated T cells. Clinical trials of two agonist antibodies, utomilumab (PF-05082566) and urelumab (BMS-663513), are ongoing in multiple cancer indications, and both antibodies demonstrate distinct activities in the clinic. To understand these differences, we solved structures of the human 4-1BB/4-1BBL complex, the 4-1BBL trimer alone, and 4-1BB bound to utomilumab or urelumab. The 4-1BB/4-1BBL complex displays a unique interaction between receptor and ligand when compared with other TNF family members. Furthermore, our ligand-only structure differs from previously published data. Utomilumab, a ligand-blocking antibody, binds 4-1BB between CRDs 3 and 4. In contrast, urelumab binds 4-1BB CRD-1, away from the ligand binding site. Finally, cell-based assays demonstrate utomilumab is a milder agonist than urelumab. Collectively, our data provide a deeper understanding of the 4-1BB signaling complex, providing a template for future development of next generation 4-1BB targeted biologics.

Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab.,Chin SM, Kimberlin CR, Roe-Zurz Z, Zhang P, Xu A, Liao-Chan S, Sen D, Nager AR, Oakdale NS, Brown C, Wang F, Yang Y, Lindquist K, Yeung YA, Salek-Ardakani S, Chaparro-Riggers J Nat Commun. 2018 Nov 8;9(1):4679. doi: 10.1038/s41467-018-07136-7. PMID:30410017^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Chin SM, Kimberlin CR, Roe-Zurz Z, Zhang P, Xu A, Liao-Chan S, Sen D, Nager AR, Oakdale NS, Brown C, Wang F, Yang Y, Lindquist K, Yeung YA, Salek-Ardakani S, Chaparro-Riggers J. Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab. Nat Commun. 2018 Nov 8;9(1):4679. doi: 10.1038/s41467-018-07136-7. PMID:30410017 doi:https://dx.doi.org/10.1038/s41467-018-07136-7

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OCA

[1] Chin SM, Kimberlin CR, Roe-Zurz Z, Zhang P, Xu A, Liao-Chan S, Sen D, Nager AR, Oakdale NS, Brown C, Wang F, Yang Y, Lindquist K, Yeung YA, Salek-Ardakani S, Chaparro-Riggers J. Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab. Nat Commun. 2018 Nov 8;9(1):4679. doi: 10.1038/s41467-018-07136-7. PMID:30410017 doi:https://dx.doi.org/10.1038/s41467-018-07136-7

[1]

@@ Line 1: / Line 1: @@
 ==Structure of the human 4-1BB / Urelumab Fab complex==
-<StructureSection load='6mhr' size='340' side='right' caption='[[6mhr]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+<StructureSection load='6mhr' size='340' side='right'caption='[[6mhr]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6mhr]] 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=6MHR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MHR FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6mhr]] 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=6MHR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MHR 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=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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]] 2.8&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6mge|6mge]], [[6mgp|6mgp]]</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=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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">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'>[https://proteopedia.org/fgij/fg.htm?mol=6mhr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mhr OCA], [https://pdbe.org/6mhr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mhr RCSB], [https://www.ebi.ac.uk/pdbsum/6mhr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mhr 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=6mhr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mhr OCA], [http://pdbe.org/6mhr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mhr RCSB], [http://www.ebi.ac.uk/pdbsum/6mhr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mhr ProSAT]</span></td></tr>
 </table>
-== Function ==
-[[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 ==
@@ Line 20: / Line 17: @@
 </div>
 <div class="pdbe-citations 6mhr" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Chin, S M]]
+[[Category: Large Structures]]
-[[Category: Kimberlin, C R]]
+[[Category: Chin SM]]
-[[Category: Roe-Zurz, Z]]
+[[Category: Kimberlin CR]]
-[[Category: Xu, A]]
+[[Category: Roe-Zurz Z]]
-[[Category: Yang, Y]]
+[[Category: Xu A]]
-[[Category: 4-1bb]]
+[[Category: Yang Y]]
-[[Category: Cd137]]
-[[Category: Complex]]
-[[Category: Immune system]]
-[[Category: Signaling]]
-[[Category: Therapeutic antibody]]
-[[Category: Tnfrsf]]

6mhr: Difference between revisions

Latest revision as of 08:08, 17 October 2024

Structure of the human 4-1BB / Urelumab Fab complex

Structural highlights

Publication Abstract from PubMed

See Also

References

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