PDBsum entry 4xbm

Signaling protein

PDB id: 4xbm

Contents

Protein chains

253 a.a.

401 a.a.

Ligands

FUC

PDB id:

4xbm

Name:

Signaling protein

Title:

X-ray crystal structure of notch ligand delta-like 1

Structure:

Delta-like protein 1. Chain: a, b. Synonym: drosophila delta homolog 1,h-delta-1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: dll1, unq146/pro172. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: 293f

Resolution:

3.20Å R-factor: 0.260 R-free: 0.284

Authors:

N.J.Kershaw,A.W.Burgess,N.L.Church,C.S.Luo,T.E.Adam

Key ref:

N.J.Kershaw et al. (2015). Notch ligand delta-like1: X-ray crystal structure and binding affinity. Biochem J, 468, 159-166. PubMed id: 25715738 DOI: 10.1042/BJ20150010

Date:

17-Dec-14 Release date: 11-Mar-15

Protein chain

O00548  (DLL1_HUMAN) -  Delta-like protein 1 from Homo sapiens

Seq: 723 a.a.

Struc: 253 a.a.

Protein chain

O00548  (DLL1_HUMAN) -  Delta-like protein 1 from Homo sapiens

Seq: 723 a.a.

Struc: 401 a.a.

DOI no: 10.1042/BJ20150010

Biochem J 468:159-166 (2015)

PubMed id: 25715738

Notch ligand delta-like1: X-ray crystal structure and binding affinity.

N.J.Kershaw, N.L.Church, M.D.Griffin, C.S.Luo, T.E.Adams, A.W.Burgess.

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.