1yc7
From Proteopedia
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[[Image:1yc7.gif|left|200px]] | [[Image:1yc7.gif|left|200px]] | ||
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'''cAbAn33 VHH fragment against VSG''' | '''cAbAn33 VHH fragment against VSG''' | ||
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[[Category: Vincke, C.]] | [[Category: Vincke, C.]] | ||
[[Category: Wyns, L.]] | [[Category: Wyns, L.]] | ||
| - | [[Category: | + | [[Category: Antibody]] |
| - | [[Category: | + | [[Category: Camel antibody]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:08:30 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 13:08, 3 May 2008
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 Page seeded by OCA on Sat May 3 16:08:30 2008
