View source for 8hxq


==Nanobody1 in complex with human BCMA ECD==
<StructureSection load='8hxq' size='340' side='right'caption='[[8hxq]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8hxq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8HXQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HXQ 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]] 2.4&#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=8hxq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hxq OCA], [https://pdbe.org/8hxq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hxq RCSB], [https://www.ebi.ac.uk/pdbsum/8hxq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hxq ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TNR17_HUMAN TNR17_HUMAN] Note=A chromosomal aberration involving TNFRSF17 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with IL2.
== Function ==
[https://www.uniprot.org/uniprot/TNR17_HUMAN TNR17_HUMAN] Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes B-cell survival and plays a role in the regulation of humoral immunity. Activates NF-kappa-B and JNK.<ref>PMID:10903733</ref> <ref>PMID:10801128</ref> <ref>PMID:10973284</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity, safeguarding receptor activation, and facilitating amplification of signal transduction across the cellular membrane. However, cell-surface antigen-induced multimerization (dubbed AIM herein) has not yet been consciously leveraged in chimeric antigen receptor (CAR) engineering for enriching T cell-based therapies. We co-developed ciltacabtagene autoleucel (cilta-cel), whose CAR incorporates two B-cell maturation antigen (BCMA)-targeted nanobodies in tandem, for treating multiple myeloma. Here we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated cytotoxicity. Crystallographic analysis of BCMA-nanobody complexes revealed atomic details of antigen-antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in solution. BCMA-induced nanobody CAR multimerization enhanced cytotoxicity, alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release, towards myeloma-derived cells. Our results provide a framework for contemplating the AIM approach in designing next-generation CARs.

Antigen-induced chimeric antigen receptor multimerization amplifies on-tumor cytotoxicity.,Sun Y, Yang XN, Yang SS, Lyu YZ, Zhang B, Liu KW, Li N, Cui JC, Huang GX, Liu CL, Xu J, Mi JQ, Chen Z, Fan XH, Chen SJ, Chen S Signal Transduct Target Ther. 2023 Dec 8;8(1):445. doi: , 10.1038/s41392-023-01686-z. PMID:38062078<ref>PMID:38062078</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8hxq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Vicugna pacos]]
[[Category: Sun Y]]
[[Category: Zhang B]]