title: Intrinsic motions in the N-terminal domain of an ionotropic glutamate receptor detected by fluorescence correlation spectroscopy.
abstract: Ionotropic glutamate receptors (iGluRs) mediate excitatory neurotransmission in the central nervous system and play key roles in brain development and disease. iGluRs have two distinct extracellular domains, but the functional role of the distal N-terminal domain (NTD) is poorly understood. Crystal structures of the NTD from some non-N-methyl-d-aspartate (NMDA) iGluRs are consistent with a rigid body that facilitates receptor assembly but suggest an additional dynamic role that could modulate signaling. Here, we moved beyond spatial and temporal limitations of conventional protein single-molecule spectroscopy by employing correlation analysis of extrinsic oxazine fluorescence fluctuations. We observed nanosecond (ns)-to-microsecond (μs) motions of loop segments and helices within a region of an AMPA-type iGluR NTD, which has been identified previously to be structurally variable. Our data reveal that the AMPA receptor NTD undergoes rapid conformational fluctuations, suggesting an inherent allosteric capacity for this domain in addition to its established assembly function.
authors: Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
authors: Mette H
authors: MH
authors: Jensen
authors: Madhav
authors: M
authors: Sukumaran
authors: Christopher M
authors: CM
authors: Johnson
authors: Ingo H
authors: IH
authors: Greger
authors: Hannes
authors: H
authors: Neuweiler
mesh_terms: D001665:Binding Sites; D006801:Humans; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018091:Receptors, AMPA / Q000378:metabolism*; D058468:Receptors, Ionotropic Glutamate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
chemical_list: D018091:Receptors, AMPA; D058468:Receptors, Ionotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate