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A model for a glutamate receptor agonist antibody‐binding site
Author(s) -
McDonald Shawn,
Carlson Noel G.,
Gahring Lorise C.,
Ely Kathryn R.,
Rogers Scott W.
Publication year - 1999
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/(sici)1099-1352(199907/08)12:4<219::aid-jmr457>3.0.co;2-3
Subject(s) - epitope , glutamate receptor , agonist , chemistry , receptor , autoantibody , peptide , mutagenesis , antibody , biochemistry , epitope mapping , linear epitope , disulfide bond , protein subunit , stereochemistry , biophysics , biology , mutation , immunology , gene
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. Copyright © 1999 John Wiley & Sons, Ltd.