1I5H

SOLUTION STRUCTURE OF THE RNEDD4 WWIII DOMAIN-RENAL BP2 PEPTIDE COMPLEX

1I5H の概要

• エントリーDOI: 10.2210/pdb1i5h/pdb
• 分子名称: UBIQUITIN LIGASE NEDD4, AMILORIDE-SENSITIVE SODIUM CHANNEL BETA-SUBUNIT (2 entities in total)
• 機能のキーワード: nedd4, ww domains, enac, py motif, liddle syndrome, proline-rich, ligase
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• 細胞内の位置: Cytoplasm: Q62940; Apical cell membrane; Multi-pass membrane protein (By similarity): P37090
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 7392.13

構造登録者

Kanelis, V.,Rotin, D.,Forman-Kay, J.D. (登録日: 2001-02-27, 公開日: 2001-05-02, 最終更新日: 2024-05-22)

主引用文献

Kanelis, V.,Rotin, D.,Forman-Kay, J.D.
Solution structure of a Nedd4 WW domain-ENaC peptide complex.
Nat.Struct.Biol., 8:407-412, 2001

PubMed Abstract: Nedd4 is a ubiquitin protein ligase composed of a C2 domain, three (or four) WW domains and a ubiquitin ligase Hect domain. Nedd4 was demonstrated to bind the epithelial sodium channel (alphabetagammaENaC), by association of its WW domains with PY motifs (XPPXY) present in each ENaC subunit, and to regulate the cell surface stability of the channel. The PY motif of betaENaC is deleted or mutated in Liddle syndrome, a hereditary form of hypertension caused by elevated ENaC activity. Here we report the solution structure of the third WW domain of Nedd4 complexed to the PY motif-containing region of betaENaC (TLPIPGTPPPNYDSL, referred to as betaP2). A polyproline type II helical conformation is adopted by the PPPN sequence. Unexpectedly, the C-terminal sequence YDSL forms a helical turn and both the tyrosine and the C-terminal leucine contact the WW domain. This is unlike other proline-rich peptides complexed to WW domains, which bind in an extended conformation and lack molecular interactions with residues C-terminal to the tyrosine or the structurally equivalent residue in non-PY motif WW domain targets. The Nedd4 WW domain-ENaC betaP2 peptide structure expands our understanding of the mechanisms involved in WW domain-ligand recognition and the molecular basis of Liddle syndrome.

PubMed: 11323714
DOI: 10.1038/87562

実験手法

SOLUTION NMR