skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Structural basis for Notch1 engagement of Delta-like 4

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. Lastly, 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.

Authors:
 [1];  [1];  [2];  [2];  [1];  [1]
  1. Stanford Univ. School of Medicine, Stanford, CA (United States). Howard Hughes Medical Inst.; Stanford Univ. School of Medicine, Stanford, CA (United States). Dept. of Molecular and Cellular Physiology; Stanford Univ. School of Medicine, Stanford, CA (United States). Dept. of Structural Biology
  2. Stanford Univ. School of Medicine, Stanford, CA (United States). Dept. of Molecular and Cellular Physiology
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Institutes of Health (NIH)
OSTI Identifier:
1182315
Grant/Contract Number:
AC02-76SF00515; NIH-1RO1-GM097015
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Science
Additional Journal Information:
Journal Volume: 347; Journal Issue: 6224; Journal ID: ISSN 0036-8075
Publisher:
AAAS
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Luca, Vincent C., Jude, Kevin M., Pierce, Nathan W., Nachury, Maxence V., Fischer, Suzanne, and Garcia, K. Christopher. Structural basis for Notch1 engagement of Delta-like 4. United States: N. p., 2015. Web. doi:10.1126/science.1261093.
Luca, Vincent C., Jude, Kevin M., Pierce, Nathan W., Nachury, Maxence V., Fischer, Suzanne, & Garcia, K. Christopher. Structural basis for Notch1 engagement of Delta-like 4. United States. doi:10.1126/science.1261093.
Luca, Vincent C., Jude, Kevin M., Pierce, Nathan W., Nachury, Maxence V., Fischer, Suzanne, and Garcia, K. Christopher. Fri . "Structural basis for Notch1 engagement of Delta-like 4". United States. doi:10.1126/science.1261093. https://www.osti.gov/servlets/purl/1182315.
@article{osti_1182315,
title = {Structural basis for Notch1 engagement of Delta-like 4},
author = {Luca, Vincent C. and Jude, Kevin M. and Pierce, Nathan W. and Nachury, Maxence V. and Fischer, Suzanne and Garcia, K. Christopher},
abstractNote = {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. Lastly, 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.},
doi = {10.1126/science.1261093},
journal = {Science},
number = 6224,
volume = 347,
place = {United States},
year = {Fri Feb 20 00:00:00 EST 2015},
month = {Fri Feb 20 00:00:00 EST 2015}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 63 works
Citation information provided by
Web of Science

Save / Share: