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| Antibody domain exchange is an immunological solution to carbohydrate cluster recognition |
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| Author(s): 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 |
| Source: SCIENCE Volume: 300 Issue: 5628 Pages: 2065-2071 Published: JUN 27 2003 |
| Times Cited: 228 References: 58 |
| 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 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Wilson, IA (reprint author), Scripps Res Inst, Dept Mol Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA |
Addresses:
1. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
2. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
3. Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA
4. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
5. Univ Oxford, Dept Biochem, Glycobiol Inst, Oxford OX1 3QU, England
6. Agr Univ Vienna, Inst Appl Microbiol, A-1180 Vienna, Austria
7. Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA
8. Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA |
| Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 694KZ |
| ISSN: 0036-8075 |
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