8V14
Structure of NRAP-1 and its role in NMDAR signaling
Summary for 8V14
| Entry DOI | 10.2210/pdb8v14/pdb |
| Descriptor | NMDA receptor auxiliary protein, CALCIUM ION (3 entities in total) |
| Functional Keywords | nmdar, nrap-1, synapse, postsynaptic, neurotransmitter, signaling protein |
| Biological source | Caenorhabditis elegans |
| Total number of polymer chains | 2 |
| Total formula weight | 36391.05 |
| Authors | Whitby, F.G.,Goodell, D.J.,Maricq, A.V.,Hill, C.P. (deposition date: 2023-11-19, release date: 2024-01-31, Last modification date: 2024-08-21) |
| Primary citation | Goodell, D.J.,Whitby, F.G.,Mellem, J.E.,Lei, N.,Brockie, P.J.,Maricq, A.J.,Eckert, D.M.,Hill, C.P.,Madsen, D.M.,Maricq, A.V. Mechanistic and structural studies reveal NRAP-1-dependent coincident activation of NMDARs. Cell Rep, 43:113694-113694, 2024 Cited by PubMed Abstract: N-methyl-D-aspartate (NMDA)-type ionotropic glutamate receptors have essential roles in neurotransmission and synaptic plasticity. Previously, we identified an evolutionarily conserved protein, NRAP-1, that is required for NMDA receptor (NMDAR) function in C. elegans. Here, we demonstrate that NRAP-1 was sufficient to gate NMDARs and greatly enhanced glutamate-mediated NMDAR gating, thus conferring coincident activation properties to the NMDAR. Intriguingly, vertebrate NMDARs-and chimeric NMDARs where the amino-terminal domain (ATD) of C. elegans NMDARs was replaced by the ATD from vertebrate receptors-were spontaneously active when ectopically expressed in C. elegans neurons. Thus, the ATD is a primary determinant of NRAP-1- and glutamate-mediated gating of NMDARs. We determined the crystal structure of NRAP-1 at 1.9-Å resolution, which revealed two distinct domains positioned around a central low-density lipoprotein receptor class A domain. The NRAP-1 structure, combined with chimeric and mutational analyses, suggests a model where the three NRAP-1 domains work cooperatively to modify the gating of NMDARs. PubMed: 38265937DOI: 10.1016/j.celrep.2024.113694 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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