3GSL
Crystal structure of PSD-95 tandem PDZ domains 1 and 2
Summary for 3GSL
| Entry DOI | 10.2210/pdb3gsl/pdb |
| Related | 2FE5 2I1N |
| Descriptor | Disks large homolog 4 (2 entities in total) |
| Functional Keywords | pdz domain, tandem, psd-95, dlg4, sap-90, glur6, cell junction, cell membrane, lipoprotein, membrane, palmitate, phosphoprotein, postsynaptic cell membrane, sh3 domain, synapse, structural protein |
| Biological source | Rattus norvegicus (rat) |
| Cellular location | Cell membrane; Peripheral membrane protein: P31016 |
| Total number of polymer chains | 2 |
| Total formula weight | 41581.31 |
| Authors | Sainlos, M.,Olivier, N.B.,Imperiali, B. (deposition date: 2009-03-27, release date: 2010-09-29, Last modification date: 2023-09-06) |
| Primary citation | Sainlos, M.,Tigaret, C.,Poujol, C.,Olivier, N.B.,Bard, L.,Breillat, C.,Thiolon, K.,Choquet, D.,Imperiali, B. Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization. Nat.Chem.Biol., 7:81-91, 2011 Cited by PubMed Abstract: The interactions of the AMPA receptor (AMPAR) auxiliary subunit Stargazin with PDZ domain-containing scaffold proteins such as PSD-95 are critical for the synaptic stabilization of AMPARs. To investigate these interactions, we have developed biomimetic competing ligands that are assembled from two Stargazin-derived PSD-95/DLG/ZO-1 (PDZ) domain-binding motifs using 'click' chemistry. Characterization of the ligands in vitro and in a cellular FRET-based model revealed an enhanced affinity for the multiple PDZ domains of PSD-95 compared to monovalent peptides. In cultured neurons, the divalent ligands competed with transmembrane AMPAR regulatory protein (TARP) for the intracellular membrane-associated guanylate kinase resulting in increased lateral diffusion and endocytosis of surface AMPARs, while showing strong inhibition of synaptic AMPAR currents. This provides evidence for a model in which the TARP-containing AMPARs are stabilized at the synapse by engaging in multivalent interactions. In light of the prevalence of PDZ domain clusters, these new biomimetic chemical tools could find broad application for acutely perturbing multivalent complexes. PubMed: 21186349DOI: 10.1038/nchembio.498 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.05 Å) |
Structure validation
Download full validation report
