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Evidence for involvement of a hydrophobic patch in framework region 1 of human V4-34-encoded Igs in recognition of the red blood cell I antigen

Record type: Article

The monoclonal IgM cold agglutinins that bind to the I/i carbohydrate Ags on the surface of RBCs all have Ig H chains encoded by the V4-34 gene segment. This mandatory use indicates that distinctive amino acid sequences may be involved in recognition. Critical amino acids exist in framework region 1 (FR1) of V4-34-encoded Ig, and these generate a specific Id determinant which apparently lies close to the I binding site. However, I binding by Id-expressing Ig can be modulated by sequences in complementarity-determining region (CDR)H3. Examination of the crystal structure of an anti-I cold agglutinin has revealed a hydrophobic patch in FR1 involving residue W7 on {beta}-strand A and the AVY motif (residues 23–25) on {beta}-strand B. In this study we used mutagenesis to show that each of the strand components of the hydrophobic patch is required for binding the I carbohydrate Ag. In addition, the crystal structure reveals that amino acids in the carboxyl-terminal region of CDRH3 form a surface region adjacent to the hydrophobic patch. We propose that the I carbohydrate Ag interacts simultaneously with the entire hydrophobic patch in FR1 and with the outside surface of CDRH3. This interaction could leave most of the conventional binding site available for binding other Ags.

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Citation

Potter, Kathleen N., Hobby, Paul, Klijn, Susanne, Stevenson, Freda K. and Sutton, Brian J. (2002) Evidence for involvement of a hydrophobic patch in framework region 1 of human V4-34-encoded Igs in recognition of the red blood cell I antigen The Journal of Immunology, 169, (7), pp. 3777-3782.

More information

Published date: 2002

Identifiers

Local EPrints ID: 26537
URI: http://eprints.soton.ac.uk/id/eprint/26537
PURE UUID: 39035e63-9268-4ac5-95ef-4baa0a70b0e6

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Date deposited: 21 Apr 2006
Last modified: 17 Jul 2017 16:07

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Contributors

Author: Paul Hobby
Author: Susanne Klijn
Author: Brian J. Sutton

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