9Y2F
Metabotropic Glutamate Receptor 7 in complex with ecto-domain of Extracellular Leucine Rich Repeat and Fibronectin Type III Domain Containing 2
Summary for 9Y2F
| Entry DOI | 10.2210/pdb9y2f/pdb |
| EMDB information | 72409 |
| Descriptor | Protein phosphatase 1 regulatory subunit 29, Metabotropic glutamate receptor 7 (2 entities in total) |
| Functional Keywords | mglur7, elfn2, gpcr, glutamate, trans-synaptic, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 280421.95 |
| Authors | Ludlam, W.G.,Chang, C.T.,Liauw, B.W.,Cho, H.J.,Sawh-Gopal, A.,Izard, T.,Bao, H.,Dunn, H.A.,Vafabakhsh, R.,Martemyanov, K.A. (deposition date: 2025-09-01, release date: 2026-08-05, Last modification date: 2026-09-16) |
| Primary citation | Ludlam, W.G.,Chang, C.T.,Cechova, K.,Liauw, B.W.,Cho, H.J.,Salar, S.,Sawh-Gopal, A.,Parvin, A.,Dhaliwal, S.K.,Dhaliwal, S.K.,Izard, T.,Bao, H.,Brown, A.M.,Dunn, H.A.,Vafabakhsh, R.,Martemyanov, K.A. Structural basis for modulation of group III mGlu receptors by transsynaptic interactions. Sci Adv, 12:eaed3793-eaed3793, 2026 Cited by PubMed Abstract: Group III metabotropic glutamate receptors (mGluRs) are critical signaling molecules that regulate strength, homeostasis, and plasticity of glutamatergic synaptic signaling. These receptors are engaged in transsynaptic interactions with extracellular leucine-rich repeat and fibronectin type III domain-containing (ELFN) cell adhesion proteins. ELFN proteins have been shown to play a critical role in regulation of activity and localization of mGluRs activity in vivo, yet the exact nature of their regulatory interaction has remained unknown. Here, we present a cryo-electron microscopy structure of the ELFN-mGluR complex. We identify a specific ELFN-binding pocket on mGluRs involved in its allosteric regulation through the network of residues affecting the orthosteric ligand binding site. We further uncover cooperativity whereby mGluR activation increases their association with ELFN proteins as a potential feedback mechanism to regulate synaptic strength. Last, we determine that disruption in mGluR-ELFN interaction is a recurring mechanism underlying several neurological conditions as we delineate their structure-functional etiology. PubMed: 42696580DOI: 10.1126/sciadv.aed3793 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.6 Å) |
Structure validation
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