1I92

STRUCTURAL BASIS OF THE NHERF PDZ1-CFTR INTERACTION

1I92 の概要

• エントリーDOI: 10.2210/pdb1i92/pdb
• 関連するPDBエントリー: 1G9O
• 分子名称: NA+/H+ EXCHANGE REGULATORY CO-FACTOR, CHLORIDE ION (3 entities in total)
• 機能のキーワード: pdz, cftr, nherf, complex, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10042.35

構造登録者

Karthikeyan, S.,Leung, T.,Ladias, J.A.A. (登録日: 2001-03-16, 公開日: 2001-06-27, 最終更新日: 2023-08-09)

主引用文献

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

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: 11304524
DOI: 10.1074/jbc.C100154200

実験手法

X-RAY DIFFRACTION (1.7 Å)