Antibody Domain Exchange Is an Immunological Solution to Carbohydrate Cluster Recognition
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- 27 June 2003
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 300 (5628) , 2065-2071
Abstract
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.Keywords
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