1yc7

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|PDB= 1yc7 |SIZE=350|CAPTION= <scene name='initialview01'>1yc7</scene>, resolution 1.6&Aring;
|PDB= 1yc7 |SIZE=350|CAPTION= <scene name='initialview01'>1yc7</scene>, resolution 1.6&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene>
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|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
|ACTIVITY=
|ACTIVITY=
|GENE=
|GENE=
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|DOMAIN=
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1yc7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yc7 OCA], [http://www.ebi.ac.uk/pdbsum/1yc7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1yc7 RCSB]</span>
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[[Category: Vincke, C.]]
[[Category: Vincke, C.]]
[[Category: Wyns, L.]]
[[Category: Wyns, L.]]
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[[Category: SO4]]
 
[[Category: antibody]]
[[Category: antibody]]
[[Category: camel antibody]]
[[Category: camel antibody]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:20:59 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:02:26 2008''

Revision as of 22:02, 30 March 2008


PDB ID 1yc7

Drag the structure with the mouse to rotate
, resolution 1.6Å
Ligands:
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



cAbAn33 VHH fragment against VSG


Overview

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.

About this Structure

1YC7 is a Single protein structure of sequence from Camelus dromedarius. Full crystallographic information is available from OCA.

Reference

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

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