2JMF
Solution structure of the Su(dx) WW4- Notch PY peptide complex
Summary for 2JMF
| Entry DOI | 10.2210/pdb2jmf/pdb |
| Related | 1TK7 |
| NMR Information | BMRB: 15016 |
| Descriptor | E3 ubiquitin-protein ligase suppressor of deltex, Neurogenic locus Notch protein (2 entities in total) |
| Functional Keywords | ww domain, notch, nmr solution, complex, ligase-signaling protein complex, ligase/signaling protein |
| Biological source | Drosophila melanogaster (fruit fly) More |
| Cellular location | Cell membrane; Single-pass type I membrane protein. Processed neurogenic locus Notch protein: Nucleus: P07207 |
| Total number of polymer chains | 2 |
| Total formula weight | 8089.98 |
| Authors | Avis, J.M.,Blankley, R.T.,Jennings, M.D.,Golovanov, A.P. (deposition date: 2006-11-05, release date: 2007-08-28, Last modification date: 2023-12-20) |
| Primary citation | Jennings, M.D.,Blankley, R.T.,Baron, M.,Golovanov, A.P.,Avis, J.M. Specificity and Autoregulation of Notch Binding by Tandem WW Domains in Suppressor of Deltex J.Biol.Chem., 282:29032-29042, 2007 Cited by PubMed Abstract: 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. PubMed: 17656366DOI: 10.1074/jbc.M703453200 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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