2jmf
From Proteopedia
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Solution structure of the Su(dx) WW4- Notch PY peptide complex
Overview
WW domains target proline-tyrosine (PY) motifs and frequently function as, tandem pairs. When studied in isolation, single WW domains are notably, promiscuous and regulatory mechanisms are undoubtedly required to ensure, selective interactions. Here, we show that the fourth WW domain (WW4) of, Suppressor of deltex, a modular Nedd4-like protein that down-regulates the, Notch receptor, is the primary mediator of a direct interaction with a, Notch-PY motif. A natural Trp to Phe substitution in WW4 reduces its, affinity for general PY sequences and enhances selective interaction with, the Notch-PY motif via compensatory specificity-determining interactions, with PY-flanking residues. When WW4 is paired with WW3, domain-domain, association, impeding proper folding, competes with Notch-PY binding to, WW4. This novel mode of autoinhibition is relieved by binding of another, ligand to WW3. Such cooperativity may facilitate the transient regulatory, interactions observed in vivo between Su(dx) and Notch in the endocytic, pathway. The highly conserved tandem arrangement of WW domains in Nedd4, proteins, and similar arrangements in more diverse proteins, suggests, domain-domain communication may be integral to regulation of their, associated cellular activities.
About this Structure
2JMF is a Protein complex structure of sequences from Drosophila melanogaster. Full crystallographic information is available from OCA.
Reference
Specificity and autoregulation of notch binding by tandem WW domains in suppressor of deltex., Jennings MD, Blankley RT, Baron M, Golovanov AP, Avis JM, J Biol Chem. 2007 Jul 26;. PMID:17656366
Page seeded by OCA on Wed Nov 21 12:37:47 2007
