4XBM

X-ray crystal structure of Notch ligand Delta-like 1

4XBM の概要

• エントリーDOI: 10.2210/pdb4xbm/pdb
• 分子名称: Delta-like protein 1, alpha-L-fucopyranose (2 entities in total)
• 機能のキーワード: ectodomain egf-like repeat ligand c2 domain, signaling protein
• 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: 115025.80

構造登録者

Kershaw, N.J.,Burgess, A.W.,Church, N.L.,Luo, C.S.,Adam, T.E. (登録日: 2014-12-17, 公開日: 2015-03-11, 最終更新日: 2024-10-23)

主引用文献

Kershaw, N.J.,Church, N.L.,Griffin, M.D.,Luo, C.S.,Adams, T.E.,Burgess, A.W.
Notch ligand delta-like1: X-ray crystal structure and binding affinity.
Biochem.J., 468:159-166, 2015

PubMed Abstract: The Notch pathway is a fundamental signalling system in most multicellular animals. We have determined the X-ray crystal structure of the extracellular domain of the Notch ligand delta-like ligand-1 (Dll-1). The structure incorporates the N-terminal C2 domain, receptor-binding DSL domain and the first six (of eight) EGF (epidermal growth factor)-like repeats, which form a highly extended conformation, confirmed by analytical ultracentrifugation. Comparison of our structure with a fragment of Jagged1 ligand allows us to dissect the similarities and differences between the ligand families. Differences in the C2 domains of Dll-1 and Jagged1 suggest their lipid-binding properties are likely to differ. A conserved hydrophobic patch on the surface of both Dll-1 and Jagged1 provides a likely receptor-interaction site that is common to both ligands. We also explore the binding affinity of Dll-1 for a fragment of Notch1 using different techniques. Apparent binding affinities vary when different techniques are used, explaining discrepancies in the literature. Using analytical ultracentrifugation, we perform for the first time binding analyses where both receptor and ligand are in solution, which confirms a Kd of 10 μM for this interaction.

PubMed: 25715738
DOI: 10.1042/BJ20150010

実験手法

X-RAY DIFFRACTION (3.2 Å)