McDonald S, Carlson N G, Gahring L C, Ely K R, Rogers S W
The Burnham Institute, La Jolla CA 92037, USA.
J Mol Recognit. 1999 Jul-Aug;12(4):219-25. doi: 10.1002/(SICI)1099-1352(199907/08)12:4<219::AID-JMR457>3.0.CO;2-3.
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.
通过诱变、计算机建模和免疫反应性相结合的方法，构建了谷氨酸受体（GluR）一部分（称为GluR3B）的结构模型，该部分可被受体激活自身抗体结合。在这个模型中，GluR3B表位位于一个反向发夹环中，该环将对抗体识别和受体激活重要的关键残基以线性排列方式置于溶剂暴露表面。环的构象由一个疏水核心稳定，该疏水核心对于表位的功能完整性至关重要。氨基端和羧基端残基的接近表明，GluR3B肽可以通过用半胱氨酸取代这些残基并形成二硫键而环化，且不会降低免疫反应性。这一预测通过实验得到证实，因为环化肽保留了完全的免疫反应性。该模型为GluR亚基特异性功能多样性以及自身抗体在神经疾病中对该区域的作用提供了深入见解。
