1I92
STRUCTURAL BASIS OF THE NHERF PDZ1-CFTR INTERACTION
Summary for 1I92
| Entry DOI | 10.2210/pdb1i92/pdb |
| Related | 1G9O |
| Descriptor | NA+/H+ EXCHANGE REGULATORY CO-FACTOR, CHLORIDE ION (3 entities in total) |
| Functional Keywords | pdz, cftr, nherf, complex, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 10042.35 |
| Authors | Karthikeyan, S.,Leung, T.,Ladias, J.A.A. (deposition date: 2001-03-16, release date: 2001-06-27, Last modification date: 2023-08-09) |
| Primary citation | Karthikeyan, S.,Leung, T.,Ladias, J.A. Structural basis of the Na+/H+ exchanger regulatory factor PDZ1 interaction with the carboxyl-terminal region of the cystic fibrosis transmembrane conductance regulator. J.Biol.Chem., 276:19683-19686, 2001 Cited by PubMed Abstract: The PDZ1 domain of the Na(+)/H(+) exchanger regulatory factor (NHERF) binds with nanomolar affinity to the carboxyl-terminal sequence QDTRL of the cystic fibrosis transmembrane conductance regulator (CFTR) and plays a central role in the cellular localization and physiological regulation of this chloride channel. The crystal structure of human NHERF PDZ1 bound to the carboxyl-terminal peptide QDTRL has been determined at 1.7-A resolution. The structure reveals the specificity and affinity determinants of the PDZ1-CFTR interaction and provides insights into carboxyl-terminal leucine recognition by class I PDZ domains. The peptide ligand inserts into the PDZ1 binding pocket forming an additional antiparallel beta-strand to the PDZ1 beta-sheet, and an extensive network of hydrogen bonds and hydrophobic interactions stabilize the complex. Remarkably, the guanido group of arginine at position -1 of the CFTR peptide forms two salt bridges and two hydrogen bonds with PDZ1 residues Glu(43) and Asn(22), respectively, providing the structural basis for the contribution of the penultimate amino acid of the peptide ligand to the affinity of the interaction. PubMed: 11304524DOI: 10.1074/jbc.C100154200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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