8vu1: Difference between revisions
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==Structure of FabS1CE3-EPR-1, an elbow-locked high affinity antibody for the erythropoeitin receptor (trigonal form)== | |||
<StructureSection load='8vu1' size='340' side='right'caption='[[8vu1]], [[Resolution|resolution]] 3.08Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8vu1]] is a 2 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=8VU1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VU1 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]] 3.08Å</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=8vu1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vu1 OCA], [https://pdbe.org/8vu1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vu1 RCSB], [https://www.ebi.ac.uk/pdbsum/8vu1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vu1 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
It has been shown previously that a set of three modifications-termed S1, Crystal Kappa, and elbow-act synergistically to improve the crystallizability of an antigen-binding fragment (Fab) framework. Here, we prepared a phage-displayed library and performed crystallization screenings to identify additional substitutions-located near the heavy-chain elbow region-which cooperate with the S1, Crystal Kappa, and elbow modifications to increase expression and improve crystallizability of the Fab framework even further. One substitution (K141Q) supports the signature Crystal Kappa-mediated Fab:Fab crystal lattice packing interaction. Another substitution (E172G) improves the compatibility of the elbow modification with the Fab framework by alleviating some of the strain incurred by the shortened and bulkier elbow linker region. A third substitution (F170W) generates a split-Fab conformation, resulting in a powerful crystal lattice packing interaction comprising the biological interaction interface between the variable heavy and light chain domains. In sum, we have used K141Q, E172G, and F170W substitutions-which complement the S1, Crystal Kappa, and elbow modifications-to generate a set of highly crystallizable Fab frameworks that can be used as chaperones to enable facile elucidation of Fab:antigen complex structures by x-ray crystallography. | |||
Antigen-binding fragments with improved crystal lattice packing and enhanced conformational flexibility at the elbow region as crystallization chaperones.,Bruce HA, Singer AU, Blazer LL, Luu K, Ploder L, Pavlenco A, Kurinov I, Adams JJ, Sidhu SS Protein Sci. 2024 Jul;33(7):e5081. doi: 10.1002/pro.5081. PMID:38924648<ref>PMID:38924648</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8vu1" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Bruce | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Sidhu | [[Category: Large Structures]] | ||
[[Category: | [[Category: Adams JJ]] | ||
[[Category: Blazer L]] | |||
[[Category: Bruce HA]] | |||
[[Category: Luu G]] | |||
[[Category: Pavlenco A]] | |||
[[Category: Ploder L]] | |||
[[Category: Sidhu SS]] | |||
[[Category: Singer AU]] | |||
Latest revision as of 11:45, 14 July 2024
Structure of FabS1CE3-EPR-1, an elbow-locked high affinity antibody for the erythropoeitin receptor (trigonal form)Structure of FabS1CE3-EPR-1, an elbow-locked high affinity antibody for the erythropoeitin receptor (trigonal form)
Structural highlights
Publication Abstract from PubMedIt has been shown previously that a set of three modifications-termed S1, Crystal Kappa, and elbow-act synergistically to improve the crystallizability of an antigen-binding fragment (Fab) framework. Here, we prepared a phage-displayed library and performed crystallization screenings to identify additional substitutions-located near the heavy-chain elbow region-which cooperate with the S1, Crystal Kappa, and elbow modifications to increase expression and improve crystallizability of the Fab framework even further. One substitution (K141Q) supports the signature Crystal Kappa-mediated Fab:Fab crystal lattice packing interaction. Another substitution (E172G) improves the compatibility of the elbow modification with the Fab framework by alleviating some of the strain incurred by the shortened and bulkier elbow linker region. A third substitution (F170W) generates a split-Fab conformation, resulting in a powerful crystal lattice packing interaction comprising the biological interaction interface between the variable heavy and light chain domains. In sum, we have used K141Q, E172G, and F170W substitutions-which complement the S1, Crystal Kappa, and elbow modifications-to generate a set of highly crystallizable Fab frameworks that can be used as chaperones to enable facile elucidation of Fab:antigen complex structures by x-ray crystallography. Antigen-binding fragments with improved crystal lattice packing and enhanced conformational flexibility at the elbow region as crystallization chaperones.,Bruce HA, Singer AU, Blazer LL, Luu K, Ploder L, Pavlenco A, Kurinov I, Adams JJ, Sidhu SS Protein Sci. 2024 Jul;33(7):e5081. doi: 10.1002/pro.5081. PMID:38924648[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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