2EZ5

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

Summary for 2EZ5

• Entry DOI: 10.2210/pdb2ez5/pdb
• Descriptor: E3 ubiquitin-protein ligase NEDD4, Commissureless LPSY Peptide (2 entities in total)
• Functional Keywords: nedd4; ww domain; commissureless; py motif; binding affinity, signalling protein, ligase
• Biological source: Drosophila melanogaster (fruit fly); More
• Cellular location: Cytoplasm: Q9VVI3; Cytoplasmic vesicle membrane; Single-pass membrane protein (Potential): Q24139
• Total number of polymer chains: 2
• Total formula weight: 6358.98

Authors

Kanelis, V.,Bruce, M.C.,Skrynnikov, N.R.,Rotin, D.,Forman-Kay, J.D. (deposition date: 2005-11-10, release date: 2006-03-28, Last modification date: 2024-05-22)

Primary citation

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

Experimental method

SOLUTION NMR