2EGN
Crystal Structure of Tamalin PDZ Domain in Complex with mGluR5 C-terminal Peptide
Summary for 2EGN
| Entry DOI | 10.2210/pdb2egn/pdb |
| Related | 2EGK 2EGO |
| Descriptor | General receptor for phosphoinositides 1-associated scaffold protein, mGluR5 C-terminal peptide (3 entities in total) |
| Functional Keywords | pdz domain, peptide complex, protein binding |
| Biological source | Rattus norvegicus (Norway rat) More |
| Cellular location | Cytoplasm, perinuclear region: Q8R4T5 |
| Total number of polymer chains | 2 |
| Total formula weight | 11123.42 |
| Authors | Sugi, T.,Oyama, T.,Muto, T.,Nakanishi, S.,Morikawa, K.,Jingami, H. (deposition date: 2007-03-01, release date: 2007-05-15, Last modification date: 2024-10-16) |
| Primary citation | Sugi, T.,Oyama, T.,Muto, T.,Nakanishi, S.,Morikawa, K.,Jingami, H. Crystal structures of autoinhibitory PDZ domain of Tamalin: implications for metabotropic glutamate receptor trafficking regulation Embo J., 26:2192-2205, 2007 Cited by PubMed Abstract: Metabotropic glutamate receptors (mGluRs) function as neuronal G-protein-coupled receptors and this requires efficient membrane targeting through associations with cytoplasmic proteins. However, the molecular mechanism regulating mGluR cell-surface trafficking remains unknown. We report here that mGluR trafficking is controlled by the autoregulatory assembly of a scaffold protein Tamalin. In the absence of mGluR, Tamalin self-assembles into autoinhibited conformations, through its PDZ domain and C-terminal intrinsic ligand motif. X-ray crystallographic analyses visualized integral parts of the oligomeric self-assemblies of Tamalin, which require not only the novel hydrophobic dimerization interface but also canonical and noncanonical PDZ/ligand autoinhibitory interactions. The mGluR cytoplasmic region can competitively bind to Tamalin at a higher concentration, disrupting weak inhibitory interactions. The atomic view of mGluR association suggests that this rearrangement is dominated by electrostatic attraction and repulsion. We also observed in mammalian cells that the association liberates the intrinsic ligand toward a motor protein receptor, thereby facilitating mGluR cell-surface trafficking. Our study suggests a novel regulatory mechanism of the PDZ domain, by which Tamalin switches between the trafficking-inhibited and -active forms depending on mGluR association. PubMed: 17396155DOI: 10.1038/sj.emboj.7601651 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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