6ffj: Difference between revisions
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The | ==Anti-tumor antibody 14F7-derived single chain fragment variable (scFv)== | ||
<StructureSection load='6ffj' size='340' side='right'caption='[[6ffj]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6ffj]] is a 4 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=6FFJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FFJ 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]] 2.2Å</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=6ffj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ffj OCA], [https://pdbe.org/6ffj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ffj RCSB], [https://www.ebi.ac.uk/pdbsum/6ffj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ffj ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Targeted cancer immunotherapy offers increased efficacy concomitantly with reduced side effects. One antibody with promising clinical potential is 14F7, which specifically recognises the NeuGc GM3 ganglioside. This antigen is found in the plasma membrane of a range of tumours, but is essentially absent from healthy human cells. 14F7 can discriminate NeuGc GM3 from the very similar NeuAc GM3, a common component of cell membranes. The molecular basis for this unique specificity is poorly understood. Here we designed and expressed 14F7-derived single-chain Fvs (scFvs), which retained the specificity of the parent antibody. Detailed expression and purification protocols are described as well as the synthesis of the NeuGc GM3 trisaccharide. The most successful scFv construct, which comprises an alternative variable light chain (VLA), allowed structure determination to 2.2 A resolution. The structure gives insights into the conformation of the important CDR H3 loop and the suspected antigen binding site. Furthermore, the presence of VLA instead of the original VL elucidates how this subdomain indirectly stabilises the CDR H3 loop. The current work may serve as a guideline for the efficient production of scFvs for structure determination. | |||
Crystal structure of an L chain optimised 14F7 anti-ganglioside Fv suggests a unique tumour-specificity through an unusual H-chain CDR3 architecture.,Bjerregaard-Andersen K, Johannesen H, Abdel-Rahman N, Heggelund JE, Hoas HM, Abraha F, Bousquet PA, Hoydahl LS, Burschowsky D, Rojas G, Oscarson S, Loset GA, Krengel U Sci Rep. 2018 Jul 18;8(1):10836. doi: 10.1038/s41598-018-28918-5. PMID:30022069<ref>PMID:30022069</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[ | </div> | ||
[[Category: | <div class="pdbe-citations 6ffj" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Bjerregaard-Andersen | ==See Also== | ||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Bjerregaard-Andersen K]] | |||
[[Category: Heggelund JE]] | |||
[[Category: Krengel U]] | |||
Latest revision as of 10:57, 17 October 2024
Anti-tumor antibody 14F7-derived single chain fragment variable (scFv)Anti-tumor antibody 14F7-derived single chain fragment variable (scFv)
Structural highlights
Publication Abstract from PubMedTargeted cancer immunotherapy offers increased efficacy concomitantly with reduced side effects. One antibody with promising clinical potential is 14F7, which specifically recognises the NeuGc GM3 ganglioside. This antigen is found in the plasma membrane of a range of tumours, but is essentially absent from healthy human cells. 14F7 can discriminate NeuGc GM3 from the very similar NeuAc GM3, a common component of cell membranes. The molecular basis for this unique specificity is poorly understood. Here we designed and expressed 14F7-derived single-chain Fvs (scFvs), which retained the specificity of the parent antibody. Detailed expression and purification protocols are described as well as the synthesis of the NeuGc GM3 trisaccharide. The most successful scFv construct, which comprises an alternative variable light chain (VLA), allowed structure determination to 2.2 A resolution. The structure gives insights into the conformation of the important CDR H3 loop and the suspected antigen binding site. Furthermore, the presence of VLA instead of the original VL elucidates how this subdomain indirectly stabilises the CDR H3 loop. The current work may serve as a guideline for the efficient production of scFvs for structure determination. Crystal structure of an L chain optimised 14F7 anti-ganglioside Fv suggests a unique tumour-specificity through an unusual H-chain CDR3 architecture.,Bjerregaard-Andersen K, Johannesen H, Abdel-Rahman N, Heggelund JE, Hoas HM, Abraha F, Bousquet PA, Hoydahl LS, Burschowsky D, Rojas G, Oscarson S, Loset GA, Krengel U Sci Rep. 2018 Jul 18;8(1):10836. doi: 10.1038/s41598-018-28918-5. PMID:30022069[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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