PXD080956-1

PXD080956 is an original dataset announced via ProteomeXchange.

Title	Distribution, assembly and mechanism of GluN1/GluN3A excitatory glycine receptors
Description	NMDA receptors play key roles in brain development, plasticity and diseases. While glutamate and glycine co-gated GluN2-containing NMDARs have been extensively characterized, little is known regarding GluN3A-containing NMDARs that form receptors gated by glycine only. Here, combining native purification, mass spectrometry, cryo-EM and electrophysiology, we provide key insights on the molecular logic of GluN3A-NMDARs. We demonstrate that native GluN3A receptors account for a sizeable fraction of total NMDARs, are enriched at extrasynaptic compartments in the adult brain, and assemble as diheteromeric GluN1/GluN3A excitatory glycine receptors (eGlyRs) rather than as triheteromeric GluN1/GluN2/GluN3A receptors. The architecture of eGlyRs reveal splayed and loosely packed extracellular domains, strikingly different from ‘conventional’ GluN1/GluN2 receptors. Through back-and-forth structural and functional validations, we demonstrate how the combined effects of a weak ligand-binding domain (LBD) dimer interface and high intrinsic mobility of the N-terminal domains (NTDs) shape the atypical gating of eGlyRs. These findings illuminate GluN3A-NMDAR physiology and mechanism, with implications for neuronal signaling and pharmacology.
HostingRepository	iProX
AnnounceDate	2026-07-13
AnnouncementXML	Submission_2026-07-13_01:43:27.412.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nan Zhao
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2026-07-13 01:43:11	ID requested
⏵ 1	2026-07-13 01:43:28	announced

Dataset with its publication pending

submitter keyword: NMDAR, GluN1/GluN3A, CryoEM, Mass Spectrometry, electrophysiology

Lihua Zhang
contact affiliation	Dalian Institute of Chemical Physics
contact email	lihuazhang@dicp.ac.cn
lab head
Nan Zhao
contact affiliation	Dalian Institute of Chemical Physics
contact email	zhaonan@dicp.ac.cn
dataset submitter

iProX dataset URI