2LUI
Structure of the PICK PDZ domain in complex with the DAT C-terminal
Summary for 2LUI
| Entry DOI | 10.2210/pdb2lui/pdb |
| NMR Information | BMRB: 18522 |
| Descriptor | PICK1 PDZ DOMAIN FUSED TO THE C10 DAT LIGAND (1 entity in total) |
| Functional Keywords | pdz, dat c-terminal, pick1, protein binding |
| Biological source | Rattus norvegicus (brown rat,rat,rats) |
| Total number of polymer chains | 1 |
| Total formula weight | 12428.33 |
| Authors | Erlendsson, S.,Rathje, M.,Heidarsson, P.O.,Poulsen, F.M.,Madsen, K.L.,Teilum, K.,Gether, U. (deposition date: 2012-06-14, release date: 2013-06-19, Last modification date: 2024-05-01) |
| Primary citation | Erlendsson, S.,Rathje, M.,Heidarsson, P.O.,Poulsen, F.M.,Madsen, K.L.,Teilum, K.,Gether, U. Protein interacting with C-kinase 1 (PICK1) binding promiscuity relies on unconventional PSD-95/discs-large/ZO-1 homology (PDZ) binding modes for nonclass II PDZ ligands. J.Biol.Chem., 289:25327-25340, 2014 Cited by PubMed Abstract: PDZ domain proteins control multiple cellular functions by governing assembly of protein complexes. It remains unknown why individual PDZ domains can bind the extreme C terminus of very diverse binding partners and maintain selectivity. By employing NMR spectroscopy, together with molecular modeling, mutational analysis, and fluorescent polarization binding experiments, we identify here three structural mechanisms explaining why the PDZ domain of PICK1 selectively binds >30 receptors, transporters, and kinases. Class II ligands, including the dopamine transporter, adopt a canonical binding mode with promiscuity obtained via differential packing in the binding groove. Class I ligands, such as protein kinase Cα, depend on residues upstream from the canonical binding sequence that are likely to interact with flexible loop residues of the PDZ domain. Finally, we obtain evidence that the unconventional ligand ASIC1a has a dual binding mode involving a canonical insertion and a noncanonical internal insertion with the two C-terminal residues forming interactions outside the groove. Together with an evolutionary analysis, the data show how unconventional binding modes might evolve for a protein recognition domain to expand the repertoire of functionally important interactions. PubMed: 25023278DOI: 10.1074/jbc.M114.548743 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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