1yc8: Difference between revisions
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New page: left|200px<br /> <applet load="1yc8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yc8, resolution 2.7Å" /> '''cAbAn33- Y37V/E44G/R... |
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== | ==cAbAn33- Y37V/E44G/R45L triple mutant== | ||
Heavy chain only antibodies of camelids bind their antigens with a single | <StructureSection load='1yc8' size='340' side='right'caption='[[1yc8]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1yc8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Camelus_dromedarius Camelus dromedarius]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YC8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YC8 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]] 2.7Å</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=1yc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yc8 OCA], [https://pdbe.org/1yc8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yc8 RCSB], [https://www.ebi.ac.uk/pdbsum/1yc8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yc8 ProSAT]</span></td></tr> | |||
</table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yc/1yc8_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1yc8 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Heavy chain only antibodies of camelids bind their antigens with a single domain, the VHH, which acquired adaptations relative to classical VHs to function in the absence of a VL partner. Additional CDR loop conformations, outside the canonical loop structures of VHs, broaden the repertoire of the antigen-binding site. The combined effects of part of the CDR3 that folds over the "former" VL binding site and framework-2 mutations to more hydrophilic amino acids, enhance the solubility of VHH domains and prevent VL pairing. cAbAn33, a VHH domain specific for the carbohydrate moiety of the variant surface glycoprotein of trypanosomes, has a short CDR3 loop that does not cover the former VL binding site as well as a VH-specific Trp47 instead of the VHH-specific Gly47. Resurfacing its framework-2 region (mutations Tyr37Val, Glu44Gly and Arg45Leu) to mimic that of a human VH restores the VL binding capacity. In solution, the humanised VHH behaves as a soluble, monomeric entity, albeit with reduced thermodynamic stability and affinity for its antigen. Comparison of the crystal structures of cAbAn33 and its humanised derivative reveals steric hindrance exerted by VHH-specific residues Tyr37 and Arg45 that prevent the VL domain pairing, whereas Glu44 and Arg45 are key elements to avoid insolubility of the domain. | |||
Antigen binding and solubility effects upon the veneering of a camel VHH in framework-2 to mimic a VH.,Conrath K, Vincke C, Stijlemans B, Schymkowitz J, Decanniere K, Wyns L, Muyldermans S, Loris R J Mol Biol. 2005 Jul 1;350(1):112-25. PMID:15913651<ref>PMID:15913651</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
<div class="pdbe-citations 1yc8" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Camelus dromedarius]] | [[Category: Camelus dromedarius]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Conrath | [[Category: Conrath K]] | ||
[[Category: Loris | [[Category: Loris R]] | ||
[[Category: Muyldermans | [[Category: Muyldermans S]] | ||
[[Category: Schymkowitz | [[Category: Schymkowitz J]] | ||
[[Category: Stijlemans | [[Category: Stijlemans B]] | ||
[[Category: Vincke | [[Category: Vincke C]] | ||
[[Category: Wyns | [[Category: Wyns L]] | ||
