Dynamics of the S1S2 glutamate binding domain of GluR2 measured using 19F NMR spectroscopy

被引:41
作者
Ahmed, H. Ahmed
Loh, Adrienne P.
Jane, David E.
Oswald, Robert E. [1 ]
机构
[1] Cornell Univ, Dept Mol Med, Ithaca, NY 14853 USA
[2] Univ Wisconsin, Dept Chem, La Crosse, WI 54601 USA
[3] Univ Bristol, Sch Med Sci, Ctr Synapt Plast, Dept Pharmacol, Bristol BS8 1TD, Avon, England
关键词
D O I
10.1074/jbc.M610077200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ionotropic glutamate receptors mediate the majority of vertebrate excitatory synaptic transmission. Although the structure of the GluR2 binding domain (S1S2) is well known (agonist binding site between two lobes), little is known about the time scales of conformational transitions or the relationship between dynamics and function. (FNMR)-F-19 (F-19-labeled tryptophan) spectroscopy was used to monitor motions in the S1S2 domain bound to ligands with varying efficacy and in the apo state. One tryptophan (Trp-671) undergoes chemical exchange in some but not all agonists, consistent with mu s-ms motion. The dynamics can be correlated to ligand affinity, and a likely source of the motion is a peptide bond capable of transiently forming hydrogen bonds across the lobe interface. Another tryptophan (Trp767) appears to monitor motions of the relative positions of the lobes and suggests that the relative orientation in the apo- and antagonist-bound forms can exchange between at least two conformations on the ms time scale.
引用
收藏
页码:12773 / 12784
页数:12
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