8dy1: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal Structure of scFv CAT2200 LH in complex with IL-17A== | |||
<StructureSection load='8dy1' size='340' side='right'caption='[[8dy1]], [[Resolution|resolution]] 2.68Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8dy1]] 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=8DY1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DY1 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=8dy1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dy1 OCA], [https://pdbe.org/8dy1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dy1 RCSB], [https://www.ebi.ac.uk/pdbsum/8dy1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dy1 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/IL17_HUMAN IL17_HUMAN] Induces stromal cells to produce proinflammatory and hematopoietic cytokines. Enhances the surface expression of ICAM1/intracellular adhesion molecule 1 in fibroblasts. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Single-chain fragment variable (scFv) domains play an important role in antibody-based therapeutic modalities, such as bispecifics, multispecifics and chimeric antigen receptor T cells or natural killer cells. However, scFv domains exhibit lower stability and increased risk of aggregation due to transient dissociation ("breathing") and inter-molecular reassociation of the two domains (VL and VH). We designed a novel strategy, referred to as stapling, that introduces two disulfide bonds between the scFv linker and the two variable domains to minimize scFv breathing. We named the resulting molecules stapled scFv (spFv). Stapling increased thermal stability (Tm) by an average of 10 degrees C. In multiple scFv/spFv multispecifics, the spFv molecules display significantly improved stability, minimal aggregation and superior product quality. These spFv multispecifics retain binding affinity and functionality. Our stapling design was compatible with all antibody variable regions we evaluated and may be widely applicable to stabilize scFv molecules for designing biotherapeutics with superior biophysical properties. | |||
"Stapling" scFv for multispecific biotherapeutics of superior properties.,Boucher LE, Prinslow EG, Feldkamp M, Yi F, Nanjunda R, Wu SJ, Liu T, Lacy ER, Jacobs S, Kozlyuk N, Del Rosario B, Wu B, Aquino P, Davidson RC, Heyne S, Mazzanti N, Testa J, Diem MD, Gorre E, Mahan A, Nanda H, Gunawardena HP, Gervais A, Armstrong AA, Teplyakov A, Huang C, Zwolak A, Chowdhury P, Cheung WC, Luo J MAbs. 2023 Jan-Dec;15(1):2195517. doi: 10.1080/19420862.2023.2195517. PMID:37074212<ref>PMID:37074212</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8dy1" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Armstrong AA]] | |||
[[Category: Luo J]] | |||
Revision as of 10:30, 3 May 2023
Crystal Structure of scFv CAT2200 LH in complex with IL-17ACrystal Structure of scFv CAT2200 LH in complex with IL-17A
Structural highlights
FunctionIL17_HUMAN Induces stromal cells to produce proinflammatory and hematopoietic cytokines. Enhances the surface expression of ICAM1/intracellular adhesion molecule 1 in fibroblasts. Publication Abstract from PubMedSingle-chain fragment variable (scFv) domains play an important role in antibody-based therapeutic modalities, such as bispecifics, multispecifics and chimeric antigen receptor T cells or natural killer cells. However, scFv domains exhibit lower stability and increased risk of aggregation due to transient dissociation ("breathing") and inter-molecular reassociation of the two domains (VL and VH). We designed a novel strategy, referred to as stapling, that introduces two disulfide bonds between the scFv linker and the two variable domains to minimize scFv breathing. We named the resulting molecules stapled scFv (spFv). Stapling increased thermal stability (Tm) by an average of 10 degrees C. In multiple scFv/spFv multispecifics, the spFv molecules display significantly improved stability, minimal aggregation and superior product quality. These spFv multispecifics retain binding affinity and functionality. Our stapling design was compatible with all antibody variable regions we evaluated and may be widely applicable to stabilize scFv molecules for designing biotherapeutics with superior biophysical properties. "Stapling" scFv for multispecific biotherapeutics of superior properties.,Boucher LE, Prinslow EG, Feldkamp M, Yi F, Nanjunda R, Wu SJ, Liu T, Lacy ER, Jacobs S, Kozlyuk N, Del Rosario B, Wu B, Aquino P, Davidson RC, Heyne S, Mazzanti N, Testa J, Diem MD, Gorre E, Mahan A, Nanda H, Gunawardena HP, Gervais A, Armstrong AA, Teplyakov A, Huang C, Zwolak A, Chowdhury P, Cheung WC, Luo J MAbs. 2023 Jan-Dec;15(1):2195517. doi: 10.1080/19420862.2023.2195517. PMID:37074212[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||