2jmf

Solution structure of the Su(dx) WW4- Notch PY peptide complexSolution structure of the Su(dx) WW4- Notch PY peptide complex

Structural highlights 2jmf is a 2 chain structure with sequence from Drosophila melanogaster. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SUDX_DROME E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Down-regulates Notch/N signaling pathway, probably by promoting Notch ubiquitination, endocytosis and degradation. Involved in wing growth and leg joint formation. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 Sep 28;282(39):29032-42. Epub 2007 Jul 26. PMID:17656366 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 2jmf Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image