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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 Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)
OSTI Identifier:
1182315
Grant/Contract Number:  
AC02-76SF00515; NIH-1RO1-GM097015
Resource Type:
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. https://doi.org/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. https://doi.org/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}
}

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Works referenced in this record:

DSL ligand endocytosis physically dissociates Notch1 heterodimers before activating proteolysis can occur
journal, February 2007

  • Nichols, James T.; Miyamoto, Alison; Olsen, Samantha L.
  • The Journal of Cell Biology, Vol. 176, Issue 4
  • DOI: 10.1083/jcb.200609014

Overview of the CCP 4 suite and current developments
journal, March 2011

  • Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
  • DOI: 10.1107/S0907444910045749

A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain
journal, April 1999

  • De Strooper, Bart; Annaert, Wim; Cupers, Philippe
  • Nature, Vol. 398, Issue 6727
  • DOI: 10.1038/19083

Fringe modulation of Jagged1-induced Notch signaling requires the action of  4galactosyltransferase-1
journal, November 2001

  • Chen, J.; Moloney, D. J.; Stanley, P.
  • Proceedings of the National Academy of Sciences, Vol. 98, Issue 24
  • DOI: 10.1073/pnas.241398098

A secreted Delta1-Fc fusion protein functions both as an activator and inhibitor of Notch1 signaling
journal, May 2002

  • Hicks, Carol; Ladi, Ena; Lindsell, Claire
  • Journal of Neuroscience Research, Vol. 68, Issue 6
  • DOI: 10.1002/jnr.10263

Collaboration gets the most out of software
journal, September 2013


Structural Analysis Uncovers Lipid-Binding Properties of Notch Ligands
journal, November 2013


Cis interactions of immunoreceptors with MHC and non-MHC ligands
journal, February 2008

  • Held, Werner; Mariuzza, Roy A.
  • Nature Reviews Immunology, Vol. 8, Issue 4
  • DOI: 10.1038/nri2278

Jagged1 signals in the postnatal subventricular zone are required for neural stem cell self-renewal
journal, September 2005


TLSMD web server for the generation of multi-group TLS models
journal, January 2006


PHENIX : building new software for automated crystallographic structure determination
journal, October 2002

  • Adams, Paul D.; Grosse-Kunstleve, Ralf W.; Hung, Li-Wei
  • Acta Crystallographica Section D Biological Crystallography, Vol. 58, Issue 11
  • DOI: 10.1107/S0907444902016657

Fringe benefits: Functional and structural impacts of O-glycosylation on the extracellular domain of Notch receptors
journal, October 2011

  • Rana, Nadia A.; Haltiwanger, Robert S.
  • Current Opinion in Structural Biology, Vol. 21, Issue 5
  • DOI: 10.1016/j.sbi.2011.08.008

A Noncommercial Dual Luciferase Enzyme Assay System for Reporter Gene Analysis
journal, June 2000

  • Dyer, Benjamin W.; Ferrer, Fernando A.; Klinedinst, Donna K.
  • Analytical Biochemistry, Vol. 282, Issue 1
  • DOI: 10.1006/abio.2000.4605

XDS
journal, January 2010

  • Kabsch, Wolfgang
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
  • DOI: 10.1107/S0907444909047337

Inference of Macromolecular Assemblies from Crystalline State
journal, September 2007


Synthetic antibodies against BRIL as universal fiducial marks for single−particle cryoEM structure determination of membrane proteins
journal, March 2020

  • Mukherjee, Somnath; Erramilli, Satchal K.; Ammirati, Mark
  • Nature Communications, Vol. 11, Issue 1
  • DOI: 10.1038/s41467-020-15363-0

The Notch Ligands Dll4 and Jagged1 Have Opposing Effects on Angiogenesis
journal, June 2009


JLigand : a graphical tool for the CCP 4 template-restraint library
journal, March 2012

  • Lebedev, Andrey A.; Young, Paul; Isupov, Michail N.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4
  • DOI: 10.1107/S090744491200251X

Fringe modulates Notch–ligand interactions
journal, June 1997

  • Panin, Vladislav M.; Papayannopoulos, Venizelos; Wilson, Richa
  • Nature, Vol. 387, Issue 6636
  • DOI: 10.1038/43191

Regulation of Notch Signaling by O-Linked Fucose
journal, December 2002


Therapeutic antibody targeting of individual Notch receptors
journal, April 2010


Structural Basis of Wnt Recognition by Frizzled
journal, May 2012


NOTCH2 Mutations Cause Alagille Syndrome, a Heterogeneous Disorder of the Notch Signaling Pathway
journal, July 2006

  • McDaniell, Ryan; Warthen, Daniel M.; Sanchez-Lara, Pedro A.
  • The American Journal of Human Genetics, Vol. 79, Issue 1
  • DOI: 10.1086/505332

Coot model-building tools for molecular graphics
journal, November 2004

  • Emsley, Paul; Cowtan, Kevin
  • Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
  • DOI: 10.1107/S0907444904019158

A Mutation in EGF Repeat-8 of Notch Discriminates Between Serrate/Jagged and Delta Family Ligands
journal, November 2012


Lysine Methylation as a Routine Rescue Strategy for Protein Crystallization
journal, November 2006


Presenilin is required for activity and nuclear access of Notch in Drosophila
journal, April 1999

  • Struhl, Gary; Greenwald, Iva
  • Nature, Vol. 398, Issue 6727
  • DOI: 10.1038/19091

Notch Signaling: Cell Fate Control and Signal Integration in Development
journal, April 1999


Structural basis for autoinhibition of Notch
journal, April 2007

  • Gordon, Wendy R.; Vardar-Ulu, Didem; Histen, Gavin
  • Nature Structural & Molecular Biology, Vol. 14, Issue 4
  • DOI: 10.1038/nsmb1227

Protein structure prediction on the Web: a case study using the Phyre server
journal, February 2009

  • Kelley, Lawrence A.; Sternberg, Michael J. E.
  • Nature Protocols, Vol. 4, Issue 3
  • DOI: 10.1038/nprot.2009.2

Fringe-mediated extension of O-linked fucose in the ligand-binding region of Notch1 increases binding to mammalian Notch ligands
journal, May 2014

  • Taylor, P.; Takeuchi, H.; Sheppard, D.
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 20
  • DOI: 10.1073/pnas.1319683111

Jagged1 ( JAG1 ) mutations in Alagille syndrome: increasing the mutation detection rate
journal, May 2006

  • Warthen, Dm; Moore, Ec; Kamath, Bm
  • Human Mutation, Vol. 27, Issue 5
  • DOI: 10.1002/humu.20310

Blockade of individual Notch ligands and receptors controls graft-versus-host disease
journal, March 2013

  • Tran, Ivy T.; Sandy, Ashley R.; Carulli, Alexis J.
  • Journal of Clinical Investigation, Vol. 123, Issue 4
  • DOI: 10.1172/JCI65477

Molecular Basis for Jagged-1/Serrate Ligand Recognition by the Notch Receptor
journal, January 2013

  • Whiteman, Pat; de Madrid, Beatriz Hernandez; Taylor, Paul
  • Journal of Biological Chemistry, Vol. 288, Issue 10
  • DOI: 10.1074/jbc.M112.428854

Notch as a Mediator of Cell Fate Determination in Hematopoiesis: Evidence and Speculation
journal, April 1999


Activating Mutations of NOTCH1 in Human T Cell Acute Lymphoblastic Leukemia
journal, October 2004


Rumi Is a CAP10 Domain Glycosyltransferase that Modifies Notch and Is Required for Notch Signaling
journal, January 2008


Isolating and engineering human antibodies using yeast surface display
journal, July 2006

  • Chao, Ginger; Lau, Wai L.; Hackel, Benjamin J.
  • Nature Protocols, Vol. 1, Issue 2
  • DOI: 10.1038/nprot.2006.94

The many facets of Notch ligands
journal, September 2008


Regulation of innate and adaptive immunity by Notch
journal, May 2013

  • Radtke, Freddy; MacDonald, H. Robson; Tacchini-Cottier, Fabienne
  • Nature Reviews Immunology, Vol. 13, Issue 6
  • DOI: 10.1038/nri3445

Notch signaling in development and disease
journal, October 2004


Jagged1 mutations in Alagille syndrome
journal, January 2000


The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands
journal, September 2005

  • Ladi, Ena; Nichols, James T.; Ge, Weihong
  • The Journal of Cell Biology, Vol. 170, Issue 6
  • DOI: 10.1083/jcb.200503113

Structural and Functional Properties of the Human Notch-1 Ligand Binding Region
journal, December 2004


Regions of Drosophila Notch That Contribute to Ligand Binding and the Modulatory Influence of Fringe
journal, June 2005

  • Xu, Aiguo; Lei, Liang; Irvine, Kenneth D.
  • Journal of Biological Chemistry, Vol. 280, Issue 34
  • DOI: 10.1074/jbc.M505569200

Crystal Structure of Reovirus Attachment Protein σ1 in Complex with Sialylated Oligosaccharides
journal, August 2011


Intrinsic Selectivity of Notch 1 for Delta-like 4 Over Delta-like 1
journal, July 2013

  • Andrawes, Marie Blanke; Xu, Xiang; Liu, Hong
  • Journal of Biological Chemistry, Vol. 288, Issue 35
  • DOI: 10.1074/jbc.M113.454850

Localization of the Delta-like-1-binding Site in Human Notch-1 and Its Modulation by Calcium Affinity
journal, February 2008

  • Cordle, Jemima; RedfieldZ, Christina; Stacey, Martin
  • Journal of Biological Chemistry, Vol. 283, Issue 17
  • DOI: 10.1074/jbc.M708424200

Mutations in NOTCH1 cause aortic valve disease
journal, July 2005

  • Garg, Vidu; Muth, Alecia N.; Ransom, Joshua F.
  • Nature, Vol. 437, Issue 7056
  • DOI: 10.1038/nature03940

Highly Conserved O -Fucose Sites Have Distinct Effects on Notch1 Function
journal, July 2005

  • Rampal, Raajit; Arboleda-Velasquez, Joseph F.; Nita-Lazar, Alexandra
  • Journal of Biological Chemistry, Vol. 280, Issue 37
  • DOI: 10.1074/jbc.M506104200

Cis-interactions between Notch and Delta generate mutually exclusive signalling states
journal, April 2010

  • Sprinzak, David; Lakhanpal, Amit; LeBon, Lauren
  • Nature, Vol. 465, Issue 7294
  • DOI: 10.1038/nature08959

The Conserved Bardet-Biedl Syndrome Proteins Assemble a Coat that Traffics Membrane Proteins to Cilia
journal, June 2010


Generation of anti-Notch antibodies and their application in blocking Notch signalling in neural stem cells
journal, September 2012


Solution structure of an EGF module pair from the Plasmodium falciparum merozoite surface protein 1 1 1Edited by P. E. Wright
journal, May 1999

  • Morgan, William D.; Birdsall, Berry; Frenkiel, Thomas A.
  • Journal of Molecular Biology, Vol. 289, Issue 1
  • DOI: 10.1006/jmbi.1999.2753

The Notch1-Dll4 signaling pathway regulates mouse postnatal lymphatic development
journal, August 2011


Cholesterol Modification of Hedgehog Signaling Proteins in Animal Development
journal, October 1996


A conserved face of the Jagged/Serrate DSL domain is involved in Notch trans-activation and cis-inhibition
journal, July 2008

  • Cordle, Jemima; Johnson, Steven; Zi Yan Tay, Joyce
  • Nature Structural & Molecular Biology, Vol. 15, Issue 8
  • DOI: 10.1038/nsmb.1457

X-Ray Diffraction data from Complex of Notch1 (EGF11-13) bound to Delta-like 4 (N-EGF2) , source of 4XLW structure
dataset, May 2015

  • Luca, Vincent C.; Jude, Kevin M.; Garcia, K. Christopher
  • SBGrid Data Bank
  • DOI: 10.15785/sbgrid/69

Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia
journal, October 1996

  • Joutel, Anne; Corpechot, Christophe; Ducros, Anne
  • Nature, Vol. 383, Issue 6602
  • DOI: 10.1038/383707a0

Fringe differentially modulates Jagged1 and Delta1 signalling through Notch1 and Notch2
journal, July 2000

  • Hicks, Carol; Johnston, Stuart H.; diSibio, Guy
  • Nature Cell Biology, Vol. 2, Issue 8
  • DOI: 10.1038/35019553

Specific EGF repeats of Notch mediate interactions with Delta and serrate: Implications for notch as a multifunctional receptor
journal, November 1991


Structural conservation of Notch receptors and ligands
journal, December 1998


Overview of the CCP4 suite and current developments.
text, January 2011

  • Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
  • Apollo - University of Cambridge Repository
  • DOI: 10.17863/cam.52322

The DynDom database of protein domain motions
journal, July 2003


Feed-back mechanisms affecting Notch activation at the dorsoventral boundary in the Drosophila wing
journal, September 1997


X-Ray Diffraction data from Complex of Notch1 (EGF11-13) bound to Delta-like 4 (N-EGF2) , source of 4XLW structure
dataset, May 2015

  • Luca, Vincent C.; Jude, Kevin M.; Garcia, K. Christopher
  • SBGrid Data Bank
  • DOI: 10.15785/sbgrid/69

Works referencing / citing this record:

Notch Signaling in Development, Tissue Homeostasis, and Disease
journal, October 2017


Receptor-mediated cell mechanosensing
journal, November 2017

  • Chen, Yunfeng; Ju, Lining; Rushdi, Muaz
  • Molecular Biology of the Cell, Vol. 28, Issue 23
  • DOI: 10.1091/mbc.e17-04-0228

Notch signalling in context
journal, August 2016

  • Bray, Sarah J.
  • Nature Reviews Molecular Cell Biology, Vol. 17, Issue 11
  • DOI: 10.1038/nrm.2016.94

Control of endothelial cell tube formation by Notch ligand intracellular domain interactions with activator protein 1 (AP-1)
journal, December 2017

  • Forghany, Zary; Robertson, Francesca; Lundby, Alicia
  • Journal of Biological Chemistry, Vol. 293, Issue 4
  • DOI: 10.1074/jbc.m117.819045

Delta-like 1 and Delta-like 4 differently require their extracellular domains for triggering Notch signaling in mice
journal, January 2020


A modifier in the 129S2/SvPasCrl genome is responsible for the viability of Notch1[12f/12f] mice
journal, October 2019


Functional genomics and gene-environment interaction highlight the complexity of congenital heart disease caused by Notch pathway variants
journal, December 2019

  • Chapman, Gavin; Moreau, Julie L. M.; I. P., Eddie
  • Human Molecular Genetics, Vol. 29, Issue 4
  • DOI: 10.1093/hmg/ddz270

Biological roles of glycans
journal, August 2016


N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A
journal, June 2016

  • Yao, Guorui; Zhang, Sicai; Mahrhold, Stefan
  • Nature Structural & Molecular Biology, Vol. 23, Issue 7
  • DOI: 10.1038/nsmb.3245

A sweet development in Notch regulation
journal, September 2017

  • Bakker, Hans; Gerardy-Schahn, Rita
  • Journal of Biological Chemistry, Vol. 292, Issue 38
  • DOI: 10.1074/jbc.h117.800102

Ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden
journal, January 2021

  • Wei, Lei; Christensen, Sean R.; Fitzgerald, Megan E.
  • Science Advances, Vol. 7, Issue 1
  • DOI: 10.1126/sciadv.abd7703

Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort
journal, July 2018

  • Meester, Josephina A. N.; Sukalo, Maja; Schröder, Kim C.
  • Human Mutation, Vol. 39, Issue 9
  • DOI: 10.1002/humu.23567

Multiple roles for O‐glycans in Notch signalling
journal, July 2018


A proactive role of water molecules in acceptor recognition by protein O-fucosyltransferase 2
journal, February 2016

  • Valero-González, Jessika; Leonhard-Melief, Christina; Lira-Navarrete, Erandi
  • Nature Chemical Biology, Vol. 12, Issue 4
  • DOI: 10.1038/nchembio.2019

The multiple roles of epidermal growth factor repeat O -glycans in animal development
journal, July 2015


Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity
journal, March 2017


The sugar code: letters and vocabulary, writers, editors and readers and biosignificance of functional glycan–lectin pairing
journal, September 2019

  • Kaltner, Herbert; Abad-Rodríguez, José; Corfield, Anthony P.
  • Biochemical Journal, Vol. 476, Issue 18
  • DOI: 10.1042/bcj20170853

The UDP-Glycosyltransferase (UGT) Superfamily: New Members, New Functions, and Novel Paradigms
journal, April 2019


Notch signaling represents an important checkpoint between follicular T-helper and canonical T-helper 2 cell fate
journal, February 2018


Structural and functional dissection of the interplay between lipid and Notch binding by human Notch ligands
journal, June 2017

  • Suckling, Richard J.; Korona, Boguslawa; Whiteman, Pat
  • The EMBO Journal, Vol. 36, Issue 15
  • DOI: 10.15252/embj.201796632

The ectodomains determine ligand function in vivo and selectivity of DLL1 and DLL4 toward NOTCH1 and NOTCH2 in vitro
journal, October 2018

  • Tveriakhina, Lena; Schuster-Gossler, Karin; Jarrett, Sanchez M.
  • eLife, Vol. 7
  • DOI: 10.7554/elife.40045

Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer
journal, May 2017

  • Lim, Jing Shan; Ibaseta, Alvaro; Fischer, Marcus M.
  • Nature, Vol. 545, Issue 7654
  • DOI: 10.1038/nature22323

Structural and biochemical differences between the Notch and the amyloid precursor protein transmembrane domains
journal, April 2017

  • Deatherage, Catherine L.; Lu, Zhenwei; Kroncke, Brett M.
  • Science Advances, Vol. 3, Issue 4
  • DOI: 10.1126/sciadv.1602794

Distinctive properties of the interactions between Notch and Notch ligands
journal, December 2019

  • Hozumi, Katsuto
  • Development, Growth & Differentiation, Vol. 62, Issue 1
  • DOI: 10.1111/dgd.12641

miRNA-30e regulates abnormal differentiation of small intestinal epithelial cells in diabetic mice by downregulating Dll4 expression
journal, January 2016

  • Shan, Ti-Dong; Ouyang, Hui; Yu, Tao
  • Cell Proliferation, Vol. 49, Issue 1
  • DOI: 10.1111/cpr.12230

Making sense out of missense mutations: Mechanistic dissection of Notch receptors through structure‐function studies in Drosophila
journal, December 2019

  • Yamamoto, Shinya
  • Development, Growth & Differentiation, Vol. 62, Issue 1
  • DOI: 10.1111/dgd.12640

Effects of Notch glycosylation on health and diseases
journal, December 2019

  • Urata, Yusuke; Takeuchi, Hideyuki
  • Development, Growth & Differentiation, Vol. 62, Issue 1
  • DOI: 10.1111/dgd.12643

Cis -activation in the Notch signaling pathway
posted_content, May 2018

  • Nandagopal, Nagarajan; Santat, Leah A.; Elowitz, Michael B.
  • bioRxiv
  • DOI: 10.1101/313171

ADAM10 controls the differentiation of the coronary arterial endothelium
journal, November 2018

  • Farber, Gregory; Parks, Matthew M.; Lustgarten Guahmich, Nicole
  • Angiogenesis, Vol. 22, Issue 2
  • DOI: 10.1007/s10456-018-9653-2

Klf4 glutamylation is required for cell reprogramming and early embryonic development in mice
journal, March 2018


Notch signalling in context.
text, January 2016


Molecular engineering strategies for visualizing low-affinity protein complexes
journal, June 2019

  • Ming, Qianqian; Gonzalez-Perez, David; Luca, Vincent C.
  • Experimental Biology and Medicine, Vol. 244, Issue 17
  • DOI: 10.1177/1535370219855401

Advances in Understanding Hair Growth
journal, January 2016


O -Glycosylation modulates the stability of epidermal growth factor-like repeats and thereby regulates Notch trafficking
journal, July 2017

  • Takeuchi, Hideyuki; Yu, Hongjun; Hao, Huilin
  • Journal of Biological Chemistry, Vol. 292, Issue 38
  • DOI: 10.1074/jbc.m117.800102

tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis
journal, February 2019


Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1
journal, September 2017


Therapeutic antibodies reveal Notch control of transdifferentiation in the adult lung
journal, November 2015

  • Lafkas, Daniel; Shelton, Amy; Chiu, Cecilia
  • Nature, Vol. 528, Issue 7580
  • DOI: 10.1038/nature15715

Receptor subtype discrimination using extensive shape complementary designed interfaces
journal, May 2019


Sialic acid mediated mechanical activation of β2 adrenergic receptors by bacterial pili
journal, October 2019


Biological functions of fucose in mammals
journal, May 2017

  • Schneider, Michael; Al-Shareffi, Esam; Haltiwanger, Robert S.
  • Glycobiology, Vol. 27, Issue 7
  • DOI: 10.1093/glycob/cwx034

Cis-activation in the Notch signaling pathway
journal, January 2019

  • Nandagopal, Nagarajan; Santat, Leah A.; Elowitz, Michael B.
  • eLife, Vol. 8
  • DOI: 10.7554/elife.37880