8v14

Structure of NRAP-1 and its role in NMDAR signaling

spinqualitylabelsall models 8v14, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8v14 is a 2 chain structure with sequence from Caenorhabditis elegans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G5EEF9_CAEEL Publication Abstract from PubMed 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-A 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. Mechanistic and structural studies reveal NRAP-1-dependent coincident activation of NMDARs.,Goodell DJ, Whitby FG, Mellem JE, Lei N, Brockie PJ, Maricq AJ, Eckert DM, Hill CP, Madsen DM, Maricq AV Cell Rep. 2024 Feb 27;43(2):113694. doi: 10.1016/j.celrep.2024.113694. Epub 2024 , Jan 23. PMID:38265937 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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