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Selected Publication:

Calarese, DA; Scanlan, CN; Zwick, MB; Deechongkit, S; Mimura, Y; Kunert, R; Zhu, P; Wormald, MR; Stanfield, RL; Roux, KH; Kelly, JW; Rudd, PM; Dwek, RA; Katinger, H; Burton, DR; Wilson, IA.
(2003): Antibody domain exchange is an immunological solution to carbohydrate cluster recognition.
Science. 2003; 300(5628):2065-2071 FullText FullText_BOKU

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 Manalpha1-2Man 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.
Authors BOKU Wien:
Katinger Hermann
Kunert Renate
Find related publications in this database (using NML MeSH Indexing)
Amino Acid Sequence -
Antibodies, Monoclonal - chemistry
Antibody Affinity - chemistry
Antibody Specificity - chemistry
Binding Sites, Antibody - chemistry
Cell Adhesion Molecules - metabolism
Centrifugation, Density Gradient - metabolism
Crystallization - metabolism
Crystallography, X-Ray - metabolism
Dimerization - metabolism
Disaccharides - chemistry
Epitopes - chemistry
HIV Antibodies - chemistry
HIV Envelope Protein gp120 - immunology
HIV-1 - immunology
Humans - immunology
Hydrogen Bonding - immunology
Immunoglobulin Fab Fragments - chemistry
Immunoglobulin Heavy Chains - chemistry
Immunoglobulin Light Chains - chemistry
Immunoglobulin Variable Region - chemistry
Lectins - chemistry
Lectins, C-Type - metabolism
Ligands - metabolism
Mannans - chemistry
Mannosides - chemistry
Models, Molecular - chemistry
Molecular Sequence Data - chemistry
Mutagenesis - chemistry
Oligosaccharides - chemistry
Protein Conformation - chemistry
Protein Structure, Tertiary - chemistry
Receptors, Cell Surface - metabolism

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