2b2x: Difference between revisions
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==VLA1 RdeltaH I-domain complexed with a quadruple mutant of the AQC2 Fab== | ==VLA1 RdeltaH I-domain complexed with a quadruple mutant of the AQC2 Fab== | ||
<StructureSection load='2b2x' size='340' side='right' caption='[[2b2x]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='2b2x' size='340' side='right'caption='[[2b2x]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2b2x]] is a 6 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2b2x]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B2X FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1mhp|1mhp]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1mhp|1mhp]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Itga1 ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Itga1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2b2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b2x OCA], [https://pdbe.org/2b2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b2x RCSB], [https://www.ebi.ac.uk/pdbsum/2b2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b2x ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/ITA1_RAT ITA1_RAT]] Integrin alpha-1/beta-1 is a receptor for laminin and collagen. It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b2/2b2x_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b2/2b2x_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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==See Also== | ==See Also== | ||
*[[3D structures of antibody|3D structures of antibody]] | *[[Antibody 3D structures|Antibody 3D structures]] | ||
*[[Integrin 3D structures|Integrin 3D structures]] | |||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Buffalo rat]] | [[Category: Buffalo rat]] | ||
[[Category: Large Structures]] | |||
[[Category: Lk3 transgenic mice]] | [[Category: Lk3 transgenic mice]] | ||
[[Category: Boriack-Sjodin, P A]] | [[Category: Boriack-Sjodin, P A]] | ||
Revision as of 14:33, 3 February 2021
VLA1 RdeltaH I-domain complexed with a quadruple mutant of the AQC2 FabVLA1 RdeltaH I-domain complexed with a quadruple mutant of the AQC2 Fab
Structural highlights
Function[ITA1_RAT] Integrin alpha-1/beta-1 is a receptor for laminin and collagen. It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedImproving the affinity of a high-affinity protein-protein interaction is a challenging problem that has practical applications in the development of therapeutic biomolecules. We used a combination of structure-based computational methods to optimize the binding affinity of an antibody fragment to the I-domain of the integrin VLA1. Despite the already high affinity of the antibody (Kd approximately 7 nM) and the moderate resolution (2.8 A) of the starting crystal structure, the affinity was increased by an order of magnitude primarily through a decrease in the dissociation rate. We determined the crystal structure of a high-affinity quadruple mutant complex at 2.2 A. The structure shows that the design makes the predicted contacts. Structural evidence and mutagenesis experiments that probe a hydrogen bond network illustrate the importance of satisfying hydrogen bonding requirements while seeking higher-affinity mutations. The large and diverse set of interface mutations allowed refinement of the mutant binding affinity prediction protocol and improvement of the single-mutant success rate. Our results indicate that structure-based computational design can be successfully applied to further improve the binding of high-affinity antibodies. Affinity enhancement of an in vivo matured therapeutic antibody using structure-based computational design.,Clark LA, Boriack-Sjodin PA, Eldredge J, Fitch C, Friedman B, Hanf KJ, Jarpe M, Liparoto SF, Li Y, Lugovskoy A, Miller S, Rushe M, Sherman W, Simon K, Van Vlijmen H Protein Sci. 2006 May;15(5):949-60. Epub 2006 Apr 5. PMID:16597831[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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