A model for a glutamate receptor agonist antibody-binding site

✍ Scribed by Shawn McDonald; Noel G. Carlson; Lorise C. Gahring; Kathryn R. Ely; Scott W. Rogers

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 376 KB
• Volume: 12
• Category: Article
• ISSN: 0952-3499
• DOI: 10.1002/(sici)1099-1352(199907/08)12:4<219::aid-jmr457>3.0.co;2-3

✦ Synopsis

A combination of mutagenesis, computer modeling and immunoreactivity has been used to develop a structural model of a segment of the glutamate receptor (GluR), termed GluR3B, which is bound by receptor-activating autoantibodies. In this model, the GluR3B epitope is located in a reverse hairpin loop that places key residues important for antibody recognition and receptor activation in a linear arrangement on the solvent-exposed surface. The conformation of the loop is stabilized by a hydrophobic core which is critical for functional integrity of the epitope. The proximity of the amino-and carboxy-terminal residues suggested that the GluR3B peptide could be cyclized without diminishing immunoreactivity through replacement of these residues with cysteines and formation of a disulfide bond. This prediction was confirmed experimentally since the cyclized peptide retained full immunoreactivity. The model provides insight into GluR subunit-specific functional diversity and the role of autoantibodies to this region in neurological disease.