| First Author | Bajaj G | Year | 2014 |
| Journal | Biochem Biophys Res Commun | Volume | 444 |
| Issue | 4 | Pages | 588-94 |
| PubMed ID | 24491550 | Mgi Jnum | J:219145 |
| Mgi Id | MGI:5619704 | Doi | 10.1016/j.bbrc.2014.01.111 |
| Citation | Bajaj G, et al. (2014) Identification of an atypical calcium-dependent calmodulin binding site on the C-terminal domain of GluN2A. Biochem Biophys Res Commun 444(4):588-94 |
| abstractText | 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 membrane-proximal 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 Ca(2+)/calmodulin binds GluN2A with high affinity (5.2+/-2.4 nM) in vitro. Direct interaction of Ca(2+)/calmodulin with GluN2A was not affected by disruption of classic sequence motifs associated with Ca(2+)/calmodulin target recognition, but was critically dependent upon Trp-1014. These findings provide new insight into the potential of Ca(2+)/calmodulin, previously considered a GluN1-binding partner, to influence NMDA receptors by direct association. |
