7o4y: Difference between revisions
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==m971 Fab in complex with anti-Kappa VHH domain== | |||
<StructureSection load='7o4y' size='340' side='right'caption='[[7o4y]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7o4y]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O4Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O4Y 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]] 1.6Å</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=7o4y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o4y OCA], [https://pdbe.org/7o4y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o4y RCSB], [https://www.ebi.ac.uk/pdbsum/7o4y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o4y ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cluster of differentiation-22 (CD22) belongs to the sialic acid-binding immunoglobulin (Ig)-like lectin family of receptors that is expressed on the surface of B cells. It has been classified as an inhibitory coreceptor for the B-cell receptor because of its function in establishing a baseline level of B-cell inhibition. The restricted expression of CD22 on B cells and its inhibitory function make it an attractive target for B-cell depletion in cases of B-cell malignancies. Genetically modified T cells with chimeric antigen receptors (CARs) derived from the m971 antibody have shown promise when used as an immunotherapeutic agent against B-cell acute lymphoblastic leukemia. A key aspect of the efficacy of this CAR-T was its ability to target a membrane-proximal epitope on the CD22 extracellular domain; however, the molecular details of m971 recognition of CD22 have thus far remained elusive. Here, we report the crystal structure of the m971 fragment antigen-binding in complex with the two most membrane-proximal Ig-like domains of CD22 (CD22(d6-d7)). The m971 epitope on CD22 resides at the most proximal Ig domain (d7) to the membrane, and the antibody paratope contains electrostatic surfaces compatible with interactions with phospholipid head groups. Together, our data identify molecular details underlying the successful transformation of an antibody epitope on CD22 into an effective CAR immunotherapeutic target. | |||
Structural details of monoclonal antibody m971 recognition of the membrane-proximal domain of CD22.,Ereno-Orbea J, Liu X, Sicard T, Kucharska I, Li W, Borovsky D, Cui H, Feng Y, Dimitrov DS, Julien JP J Biol Chem. 2021 Aug;297(2):100966. doi: 10.1016/j.jbc.2021.100966. Epub 2021 , Jul 14. PMID:34273351<ref>PMID:34273351</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Ereno-Orbea | <div class="pdbe-citations 7o4y" style="background-color:#fffaf0;"></div> | ||
[[Category: Julien | |||
[[Category: Sicard | ==See Also== | ||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Lama glama]] | |||
[[Category: Large Structures]] | |||
[[Category: Ereno-Orbea J]] | |||
[[Category: Julien JP]] | |||
[[Category: Sicard T]] | |||
Latest revision as of 15:44, 1 February 2024
m971 Fab in complex with anti-Kappa VHH domainm971 Fab in complex with anti-Kappa VHH domain
Structural highlights
Publication Abstract from PubMedCluster of differentiation-22 (CD22) belongs to the sialic acid-binding immunoglobulin (Ig)-like lectin family of receptors that is expressed on the surface of B cells. It has been classified as an inhibitory coreceptor for the B-cell receptor because of its function in establishing a baseline level of B-cell inhibition. The restricted expression of CD22 on B cells and its inhibitory function make it an attractive target for B-cell depletion in cases of B-cell malignancies. Genetically modified T cells with chimeric antigen receptors (CARs) derived from the m971 antibody have shown promise when used as an immunotherapeutic agent against B-cell acute lymphoblastic leukemia. A key aspect of the efficacy of this CAR-T was its ability to target a membrane-proximal epitope on the CD22 extracellular domain; however, the molecular details of m971 recognition of CD22 have thus far remained elusive. Here, we report the crystal structure of the m971 fragment antigen-binding in complex with the two most membrane-proximal Ig-like domains of CD22 (CD22(d6-d7)). The m971 epitope on CD22 resides at the most proximal Ig domain (d7) to the membrane, and the antibody paratope contains electrostatic surfaces compatible with interactions with phospholipid head groups. Together, our data identify molecular details underlying the successful transformation of an antibody epitope on CD22 into an effective CAR immunotherapeutic target. Structural details of monoclonal antibody m971 recognition of the membrane-proximal domain of CD22.,Ereno-Orbea J, Liu X, Sicard T, Kucharska I, Li W, Borovsky D, Cui H, Feng Y, Dimitrov DS, Julien JP J Biol Chem. 2021 Aug;297(2):100966. doi: 10.1016/j.jbc.2021.100966. Epub 2021 , Jul 14. PMID:34273351[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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