1I5H

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

Summary for 1I5H

• Entry DOI: 10.2210/pdb1i5h/pdb
• Descriptor: UBIQUITIN LIGASE NEDD4, AMILORIDE-SENSITIVE SODIUM CHANNEL BETA-SUBUNIT (2 entities in total)
• Functional Keywords: nedd4, ww domains, enac, py motif, liddle syndrome, proline-rich, ligase
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Cytoplasm: Q62940; Apical cell membrane; Multi-pass membrane protein (By similarity): P37090
• Total number of polymer chains: 2
• Total formula weight: 7392.13

Authors

Kanelis, V.,Rotin, D.,Forman-Kay, J.D. (deposition date: 2001-02-27, release date: 2001-05-02, Last modification date: 2024-05-22)

Primary citation

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

Experimental method

SOLUTION NMR