5mvx
From Proteopedia
Human DLL4 C2-EGF3
Structural highlights
DiseaseDLL4_HUMAN The disease is caused by mutations affecting the gene represented in this entry. FunctionDLL4_HUMAN Involved in the Notch signaling pathway as Notch ligand (PubMed:11134954). Activates NOTCH1 and NOTCH4. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting (PubMed:20616313). Essential for retinal progenitor proliferation. Required for suppressing rod fates in late retinal progenitors as well as for proper generation of other retinal cell types (By similarity). During spinal cord neurogenesis, inhibits V2a interneuron fate (PubMed:17728344).[UniProtKB:Q9JI71][1] [2] [3] Publication Abstract from PubMedRecent data have expanded our understanding of Notch signalling by identifying a C2 domain at the N-terminus of Notch ligands, which has both lipid- and receptor-binding properties. We present novel structures of human ligands Jagged2 and Delta-like4 and human Notch2, together with functional assays, which suggest that ligand-mediated coupling of membrane recognition and Notch binding is likely to be critical in establishing the optimal context for Notch signalling. Comparisons between the Jagged and Delta family show a huge diversity in the structures of the loops at the apex of the C2 domain implicated in membrane recognition and Jagged1 missense mutations, which affect these loops and are associated with extrahepatic biliary atresia, lead to a loss of membrane recognition, but do not alter Notch binding. Taken together, these data suggest that C2 domain binding to membranes is an important element in tuning ligand-dependent Notch signalling in different physiological contexts. Structural and functional dissection of the interplay between lipid and Notch binding by human Notch ligands.,Suckling RJ, Korona B, Whiteman P, Chillakuri C, Holt L, Handford PA, Lea SM EMBO J. 2017 Aug 1;36(15):2204-2215. doi: 10.15252/embj.201796632. Epub 2017 Jun , 1. PMID:28572448[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
