2EZ5

Solution Structure of the dNedd4 WW3* Domain- Comm LPSY Peptide Complex

2EZ5 の概要

• エントリーDOI: 10.2210/pdb2ez5/pdb
• 分子名称: E3 ubiquitin-protein ligase NEDD4, Commissureless LPSY Peptide (2 entities in total)
• 機能のキーワード: nedd4; ww domain; commissureless; py motif; binding affinity, signalling protein, ligase
• 由来する生物種: Drosophila melanogaster (fruit fly); 詳細
• 細胞内の位置: Cytoplasm: Q9VVI3; Cytoplasmic vesicle membrane; Single-pass membrane protein (Potential): Q24139
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 6358.98

構造登録者

Kanelis, V.,Bruce, M.C.,Skrynnikov, N.R.,Rotin, D.,Forman-Kay, J.D. (登録日: 2005-11-10, 公開日: 2006-03-28, 最終更新日: 2024-05-22)

主引用文献

Kanelis, V.,Bruce, M.C.,Skrynnikov, N.R.,Rotin, D.,Forman-Kay, J.D.
Structural Determinants for High-Affinity Binding in a Nedd4 WW3(*) Domain-Comm PY Motif Complex
Structure, 14:543-553, 2006

PubMed Abstract: Interactions between the WW domains of Drosophila Nedd4 (dNedd4) and Commissureless (Comm) PY motifs promote axon crossing at the CNS midline and muscle synaptogenesis. Here we report the solution structure of the dNedd4 WW3* domain complexed to the second PY motif (227'TGLPSYDEALH237') of Comm. Unexpectedly, there are interactions between WW3* and ligand residues both N- and C-terminal to the PY motif. Residues Y232'-L236' form a helical turn, following the PPII helical PY motif. Mutagenesis and binding studies confirm the importance of these extensive contacts, not simultaneously observed in other WW domain complexes, and identify a variable loop in WW3* responsible for its high-affinity interaction. These studies expand our general understanding of the molecular determinants involved in WW domain-ligand recognition. In addition, they provide insights into the specific regulation of dNedd4-mediated ubiquitination of Comm and subsequent internalization of Comm or the Comm/Roundabout complex, critical for CNS and muscle development.

PubMed: 16531238
DOI: 10.1016/j.str.2005.11.018

実験手法

SOLUTION NMR