Notch ligand delta-like1: X-ray crystal structure and binding affinity
Nadia J Kershaw, Nicole L Church, Michael DW Griffin, Cindy S Luo, Timothy E Adams, Antony W Burgess
BIOCHEMICAL JOURNAL | PORTLAND PRESS LTD | Published : 2015
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 d..View full abstract
Awarded by National Health and Medical Research Council of Australia (NHMRC)
Awarded by Australian Research Council
This work was supported by the National Health and Medical Research Council of Australia (NHMRC) programme [grant number 487922]; the Ludwig Institute for Cancer Research; The Victorian State Government Operational Infrastructure Support Grant; the NHMRC Independent Research Institutes Infrastructure Support Scheme; the C.R. Roper Fellowship to M.D.W.G.; and the Australian Research Council Future Fellowship [grant number FT140100544 (to M.D.W.G.)].