Antibody Domain Exchange Is an Immunological Solution to Carbohydrate Cluster Recognition
Copyright policy )Antibody Domain Exchange Is an Immunological Solution to Carbohydrate Cluster Recognition
Human antibody 2G12 neutralizes a broad range of human immunodeficiency virus type 1 (HIV-1) isolates by binding an unusually dense cluster of carbohydrate moieties on the “silent†face of the gp120 envelope glycoprotein. Crystal structures of Fab 2G12 and its complexes with the disaccharide Manα1-2Man and with the oligosaccharide Man 9 GlcNAc 2 revealed that two Fabs assemble into an interlocked V H domain-swapped dimer. Further biochemical, biophysical, and mutagenesis data strongly support a Fab-dimerized antibody as the prevalent form that recognizes gp120. The extraordinary configuration of this antibody provides an extended surface, with newly described binding sites, for multivalent interaction with a conserved cluster of oligomannose type sugars on the surface of gp120. The unique interdigitation of Fab domains within an antibody uncovers a previously unappreciated mechanism for high-affinity recognition of carbohydrate or other repeating epitopes on cell or microbial surfaces.
- Scripps Research Institute United States
- University of Oxford United Kingdom
Antibody Affinity, Antibodies, Monoclonal, Hydrogen Bonding, HIV Antibodies, HIV Envelope Protein gp120, Crystallography, X-Ray, Disaccharides, Epitopes, Immunoglobulin Fab Fragments, Antibody Specificity, Centrifugation, Density Gradient, HIV-1, Humans, Immunoglobulin Light Chains, Amino Acid Sequence, Binding Sites, Antibody, Crystallization, Immunoglobulin Heavy Chains, Cell Adhesion Molecules, Dimerization
Antibody Affinity, Antibodies, Monoclonal, Hydrogen Bonding, HIV Antibodies, HIV Envelope Protein gp120, Crystallography, X-Ray, Disaccharides, Epitopes, Immunoglobulin Fab Fragments, Antibody Specificity, Centrifugation, Density Gradient, HIV-1, Humans, Immunoglobulin Light Chains, Amino Acid Sequence, Binding Sites, Antibody, Crystallization, Immunoglobulin Heavy Chains, Cell Adhesion Molecules, Dimerization
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