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https://ir.library.oregonstate.edu/concern/articles/w9505224w

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  • N-methyl-D-aspartate (NMDA) receptors are calcium-permeable ion channels assembled from four subunits that each have a common membrane topology. The intracellular carboxyl terminal domain (CTD) of each subunit varies in length, is least conserved between subunits, and binds multiple intracellular proteins. We defined a region of interest in the GluN2A CTD, downstream of well-characterized membraneproximal motifs, that shares only 29% sequence similarity with the equivalent region of GluN2B. GluN2A (amino acids 875-1029) was fused to GST and used as a bait to identify proteins from mouse brain with the potential to bind GluN2A as a function of calcium. Using mass spectrometry we identified calmodulin as a calcium-dependent GluN2A binding partner. Equilibrium fluorescence spectroscopy experiments indicate that Ca²⁺/calmodulin binds GluN2A with high affinity (5.2 ± 2.4 nM) in vitro. Direct interaction of Ca²⁺/calmodulin with GluN2A was not affected by disruption of classic sequence motifs associated with Ca²⁺/calmodulin target recognition, but was critically dependent upon Trp-1014. These findings provide new insight into the potential of Ca²⁺/calmodulin, previously considered a GluN1-binding partner, to influence NMDA receptors by direct association.
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  • description.provenance : Submitted by Erin Clark (erin.clark@oregonstate.edu) on 2014-07-10T16:55:49Z No. of bitstreams: 1 IshmaelJanePharmacyIdentificationAtypicalCalcium.pdf: 734123 bytes, checksum: 1c1ca274a2c92221ef14d2a07e6b81e7 (MD5)
  • description.provenance : Approved for entry into archive by Erin Clark(erin.clark@oregonstate.edu) on 2014-07-10T16:56:07Z (GMT) No. of bitstreams: 1 IshmaelJanePharmacyIdentificationAtypicalCalcium.pdf: 734123 bytes, checksum: 1c1ca274a2c92221ef14d2a07e6b81e7 (MD5)
  • description.provenance : Made available in DSpace on 2014-07-10T16:56:07Z (GMT). No. of bitstreams: 1 IshmaelJanePharmacyIdentificationAtypicalCalcium.pdf: 734123 bytes, checksum: 1c1ca274a2c92221ef14d2a07e6b81e7 (MD5) Previous issue date: 2014-02-21

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