7ALK

Structure of Drosophila C2-DSL-EGF1

7ALK の概要

• エントリーDOI: 10.2210/pdb7alk/pdb
• 分子名称: Neurogenic locus protein delta, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: delta notch ligand c2, dsl and egf domains, signaling protein
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27918.86

構造登録者

Suckling, R.,Johnson, S.,Lea, S.M. (登録日: 2020-10-06, 公開日: 2021-08-04, 最終更新日: 2024-11-13)

主引用文献

Martins, T.,Meng, Y.,Korona, B.,Suckling, R.,Johnson, S.,Handford, P.A.,Lea, S.M.,Bray, S.J.
The conserved C2 phospholipid-binding domain in Delta contributes to robust Notch signalling.
Embo Rep., 22:e52729-e52729, 2021

PubMed Abstract: Accurate Notch signalling is critical for development and homeostasis. Fine-tuning of Notch-ligand interactions has substantial impact on signalling outputs. Recent structural studies have identified a conserved N-terminal C2 domain in human Notch ligands which confers phospholipid binding in vitro. Here, we show that Drosophila ligands Delta and Serrate adopt the same C2 domain structure with analogous variations in the loop regions, including the so-called β1-2 loop that is involved in phospholipid binding. Mutations in the β1-2 loop of the Delta C2 domain retain Notch binding but have impaired ability to interact with phospholipids in vitro. To investigate its role in vivo, we deleted five residues within the β1-2 loop of endogenous Delta. Strikingly, this change compromises ligand function. The modified Delta enhances phenotypes produced by Delta loss-of-function alleles and suppresses that of Notch alleles. As the modified protein is present on the cell surface in normal amounts, these results argue that C2 domain phospholipid binding is necessary for robust signalling in vivo fine-tuning the balance of trans and cis ligand-receptor interactions.

PubMed: 34347930
DOI: 10.15252/embr.202152729

実験手法

X-RAY DIFFRACTION (3 Å)