4XLW

Complex of Notch1 (EGF11-13) bound to Delta-like 4 (N-EGF2)

Summary for 4XLW

• Entry DOI: 10.2210/pdb4xlw/pdb
• Related: 4XL1
• Descriptor: Neurogenic locus notch homolog protein 1, Delta-like protein, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: glycosylation, egf domains, receptor-ligand complex, protein binding
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 8
• Total formula weight: 175246.31

Authors

Luca, V.C.,Jude, K.M.,Garcia, K.C. (deposition date: 2015-01-13, release date: 2015-03-04, Last modification date: 2020-07-29)

Primary citation

Luca, V.C.,Jude, K.M.,Pierce, N.W.,Nachury, M.V.,Fischer, S.,Garcia, K.C.
Structural biology. Structural basis for Notch1 engagement of Delta-like 4.
Science, 347:847-853, 2015

PubMed Abstract: Notch receptors guide mammalian cell fate decisions by engaging the proteins Jagged and Delta-like (DLL). The 2.3 angstrom resolution crystal structure of the interacting regions of the Notch1-DLL4 complex reveals a two-site, antiparallel binding orientation assisted by Notch1 O-linked glycosylation. Notch1 epidermal growth factor-like repeats 11 and 12 interact with the DLL4 Delta/Serrate/Lag-2 (DSL) domain and module at the N-terminus of Notch ligands (MNNL) domains, respectively. Threonine and serine residues on Notch1 are functionalized with O-fucose and O-glucose, which act as surrogate amino acids by making specific, and essential, contacts to residues on DLL4. The elucidation of a direct chemical role for O-glycans in Notch1 ligand engagement demonstrates how, by relying on posttranslational modifications of their ligand binding sites, Notch proteins have linked their functional capacity to developmentally regulated biosynthetic pathways.

PubMed: 25700513
DOI: 10.1126/science.1261093

Experimental method

X-RAY DIFFRACTION (3.39 Å)