4CBZ

Notch ligand, Jagged-1, contains an N-terminal C2 domain

4CBZ の概要

• エントリーDOI: 10.2210/pdb4cbz/pdb
• 関連するPDBエントリー: 4CC0 4CC1
• 分子名称: PROTEIN JAGGED-1, 2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-L-fucopyranose, ... (4 entities in total)
• 機能のキーワード: signaling protein, signalling, glycoprotein, extracellular, developmental protein, notch signaling pathway, egf-like domain transmembrane, egf-like domain, disease mutation
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70234.07

構造登録者

Chilakuri, C.R.,Sheppard, D.,Ilagan, M.X.G.,Holt, L.R.,Abbott, F.,Liang, S.,Kopan, R.,Handford, P.A.,Lea, S.M. (登録日: 2013-10-17, 公開日: 2013-11-27, 最終更新日: 2024-11-13)

主引用文献

Chilakuri, C.R.,Sheppard, D.,Ilagan, M.X.G.,Holt, L.R.,Abbott, F.,Liang, S.,Kopan, R.,Handford, P.A.,Lea, S.M.
Structural Analysis Uncovers Lipid-Binding Properties of Notch Ligands
Cell Rep., 5:861-, 2013

PubMed Abstract: The Notch pathway is a core cell-cell signaling system in metazoan organisms with key roles in cell-fate determination, stem cell maintenance, immune system activation, and angiogenesis. Signals are initiated by extracellular interactions of the Notch receptor with Delta/Serrate/Lag-2 (DSL) ligands, whose structure is highly conserved throughout evolution. To date, no structure or activity has been associated with the extreme N termini of the ligands, even though numerous mutations in this region of Jagged-1 ligand lead to human disease. Here, we demonstrate that the N terminus of human Jagged-1 is a C2 phospholipid recognition domain that binds phospholipid bilayers in a calcium-dependent fashion. Furthermore, we show that this activity is shared by a member of the other class of Notch ligands, human Delta-like-1, and the evolutionary distant Drosophila Serrate. Targeted mutagenesis of Jagged-1 C2 domain residues implicated in calcium-dependent phospholipid binding leaves Notch interactions intact but can reduce Notch activation. These results reveal an important and previously unsuspected role for phospholipid recognition in control of this key signaling system.

PubMed: 24239355
DOI: 10.1016/J.CELREP.2013.10.029

実験手法

X-RAY DIFFRACTION (2.5 Å)