1yc7
From Proteopedia
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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 with SO4 as ligand. 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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