The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation

Xu, Kai; Olsen, Olav; Tzvetkova-Robev, Dorothea; Tessier-Lavigne, Marc; Nikolov, Dimitar B.

doi:10.1101/gad.257675.114

Title: The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation

Journal Article · Thu Apr 02 00:00:00 EDT 2015 · Genes & Development

DOI:https://doi.org/10.1101/gad.257675.114· OSTI ID:1178473

Xu, Kai ^[1]; Olsen, Olav ^[2]; Tzvetkova-Robev, Dorothea ^[1]; Tessier-Lavigne, Marc ^[2]; Nikolov, Dimitar B. ^[1]

Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Structural Biology Program
Rockefeller Univ., New York, NY (United States). Lab. of Brain Development and Repair

The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6 ectodomain in complex with the E2 domain of APP and show that it supports a model for APP-induced dimerization and activation of cell surface DR6.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Inst. of Health (NIH) (United States)

Contributing Organization:: Rockefeller Univ., New York, NY (United States)

Grant/Contract Number:: AC02-06CH11357; 1R01NS089786; P41 GM103403

OSTI ID:: 1178473

Journal Information:: Genes & Development, Vol. 29, Issue 8; ISSN 0890-9369

Publisher:: Cold Springs Harbor PressCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

Citation Metrics:

Cited by: 17 works

Citation information provided by
Web of Science

References (29)

PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
γ-Secretase Inhibition Reduces Spine DensityIn Vivovia an Amyloid Precursor Protein-Dependent Pathway Bittner, Tobias; Fuhrmann, Martin; Burgold, Steffen The Journal of Neuroscience, Vol. 29, Issue 33 https://doi.org/10.1523/JNEUROSCI.2288-09.2009	journal	August 2009
Three is better than one: Pre-ligand receptor assembly in the regulation of TNF receptor signaling Chan, Francis Ka-Ming Cytokine, Vol. 37, Issue 2 https://doi.org/10.1016/j.cyto.2007.03.005	journal	February 2007
Analysis of the Overall Structure of the Multi-Domain Amyloid Precursor Protein (APP) Coburger, Ina; Dahms, Sven O.; Roeser, Dirk PLoS ONE, Vol. 8, Issue 12 https://doi.org/10.1371/journal.pone.0081926	journal	December 2013
The structural biology of the amyloid precursor protein APP – a complex puzzle reveals its multi-domain architecture Coburger, Ina; Hoefgen, Sandra; Than, Manuel E. Biological Chemistry, Vol. 395, Issue 5 https://doi.org/10.1515/hsz-2013-0280	journal	February 2014
Structure and biochemical analysis of the heparin-induced E1 dimer of the amyloid precursor protein Dahms, S. O.; Hoefgen, S.; Roeser, D. Proceedings of the National Academy of Sciences, Vol. 107, Issue 12 https://doi.org/10.1073/pnas.0911326107	journal	March 2010
Metal Binding Dictates Conformation and Function of the Amyloid Precursor Protein (APP) E2 Domain Dahms, Sven O.; Könnig, Ina; Roeser, Dirk Journal of Molecular Biology, Vol. 416, Issue 3 https://doi.org/10.1016/j.jmb.2011.12.057	journal	February 2012
Toward the Treatment and Prevention of Alzheimer's Disease: Rational Strategies and Recent Progress Gandy, Sam; DeKosky, Steven T. Annual Review of Medicine, Vol. 64, Issue 1 https://doi.org/10.1146/annurev-med-092611-084441	journal	January 2013
Heparin induced dimerization of APP is primarily mediated by E1 and regulated by its acidic domain Hoefgen, Sandra; Coburger, Ina; Roeser, Dirk Journal of Structural Biology, Vol. 187, Issue 1 https://doi.org/10.1016/j.jsb.2014.05.006	journal	July 2014
Structural Characterization of the E2 Domain of APL-1, a Caenorhabditis elegans Homolog of Human Amyloid Precursor Protein, and Its Heparin Binding Site Hoopes, James T.; Liu, Xuying; Xu, Xiaomeng Journal of Biological Chemistry, Vol. 285, Issue 3 https://doi.org/10.1074/jbc.M109.018432	journal	January 2010
Agonist antibody activates death receptor 6 downstream signaling involving TRADD recruitment Hu, Rui; Du, Qiumei; Yin, Xiangyun FEBS Letters, Vol. 588, Issue 3 https://doi.org/10.1016/j.febslet.2013.12.010	journal	December 2013
TNF? and the TNF receptor superfamily: Structure-function relationship(s) Idriss, Haitham T.; Naismith, James H. Microscopy Research and Technique, Vol. 50, Issue 3 https://doi.org/10.1002/1097-0029(20000801)50:3<184::AID-JEMT2>3.0.CO;2-H	journal	January 2000
A Death Receptor 6-Amyloid Precursor Protein Pathway Regulates Synapse Density in the Mature CNS But Does Not Contribute to Alzheimer's Disease-Related Pathophysiology in Murine Models Kallop, Dara Y.; Meilandt, William J.; Gogineni, Alvin The Journal of Neuroscience, Vol. 34, Issue 19 https://doi.org/10.1523/JNEUROSCI.4963-13.2014	journal	May 2014
Kinesin-mediated axonal transport of a membrane compartment containing β-secretase and presenilin-1 requires APP Kamal, Adeela; Almenar-Queralt, Angels; LeBlanc, James F. Nature, Vol. 414, Issue 6864 https://doi.org/10.1038/414643a	journal	December 2001
The Crystal Structure of Death Receptor 6 (DR6): A Potential Receptor of the Amyloid Precursor Protein (APP) Kuester, Miriam; Kemmerzehl, Steffen; Dahms, Sven O. Journal of Molecular Biology, Vol. 409, Issue 2 https://doi.org/10.1016/j.jmb.2011.03.048	journal	June 2011
The E2 Domains of APP and APLP1 Share a Conserved Mode of Dimerization Lee, Sangwon; Xue, Yi; Hu, Jian Biochemistry, Vol. 50, Issue 24 https://doi.org/10.1021/bi101846x	journal	May 2011
A second cytotoxic proteolytic peptide derived from amyloid β-protein precursor Lu, Daniel C.; Rabizadeh, Shahrooz; Chandra, Sreeganga Nature Medicine, Vol. 6, Issue 4 https://doi.org/10.1038/74656	journal	April 2000
Solving structures of protein complexes by molecular replacement with Phaser McCoy, Airlie J. Acta Crystallographica Section D Biological Crystallography, Vol. 63, Issue 1 https://doi.org/10.1107/S0907444906045975	journal	December 2006
APP binds DR6 to trigger axon pruning and neuron death via distinct caspases Nikolaev, Anatoly; McLaughlin, Todd; O’Leary, Dennis D. M. Nature, Vol. 457, Issue 7232 https://doi.org/10.1038/nature07767	journal	February 2009
Genetic Analysis Reveals that Amyloid Precursor Protein and Death Receptor 6 Function in the Same Pathway to Control Axonal Pruning Independent of β-Secretase Olsen, Olav; Kallop, Dara Y.; McLaughlin, Todd The Journal of Neuroscience, Vol. 34, Issue 19 https://doi.org/10.1523/JNEUROSCI.3522-13.2014	journal	May 2014
NMRPipe: A multidimensional spectral processing system based on UNIX pipes Delaglio, Frank; Grzesiek, Stephan; Vuister, GeertenW. Journal of Biomolecular NMR, Vol. 6, Issue 3 https://doi.org/10.1007/BF00197809	journal	November 1995
Identification and functional characterization of DR6, a novel death domain-containing TNF receptor Pan, Guohua; Bauer, Johannes H.; Haridas, Valsala FEBS Letters, Vol. 431, Issue 3 https://doi.org/10.1016/S0014-5793(98)00791-1	journal	July 1998
Synapse Formation and Function Is Modulated by the Amyloid Precursor Protein Priller, Christina; Bauer, Thomas; Mitteregger, Gerda The Journal of Neuroscience, Vol. 26, Issue 27 https://doi.org/10.1523/JNEUROSCI.1450-06.2006	journal	July 2006
S-SAD phasing study of death receptor 6 and its solution conformation revealed by SAXS Ru, Heng; Zhao, Lixia; Ding, Wei Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 5 https://doi.org/10.1107/S0907444912004490	journal	April 2012
Alzheimer's Disease Selkoe, D. J. Cold Spring Harbor Perspectives in Biology, Vol. 3, Issue 7 https://doi.org/10.1101/cshperspect.a004457	journal	May 2011
The X-Ray Structure of an Antiparallel Dimer of the Human Amyloid Precursor Protein E2 Domain Wang, Yongcheng; Ha, Ya Molecular Cell, Vol. 15, Issue 3 https://doi.org/10.1016/j.molcel.2004.06.037	journal	August 2004
Presynaptic and Postsynaptic Interaction of the Amyloid Precursor Protein Promotes Peripheral and Central Synaptogenesis Wang, Z.; Wang, B.; Yang, L. Journal of Neuroscience, Vol. 29, Issue 35 https://doi.org/10.1523/JNEUROSCI.2132-09.2009	journal	September 2009
Crystal structure of amyloid precursor-like protein 1 and heparin complex suggests a dual role of heparin in E2 dimerization Xue, Yi; Lee, Sangwon; Ha, Ya Proceedings of the National Academy of Sciences, Vol. 108, Issue 39 https://doi.org/10.1073/pnas.1103407108	journal	September 2011
Crystal Structure of the E2 Domain of Amyloid Precursor Protein-like Protein 1 in Complex with Sucrose Octasulfate Xue, Yi; Lee, Sangwon; Wang, Yongcheng Journal of Biological Chemistry, Vol. 286, Issue 34 https://doi.org/10.1074/jbc.M111.219659	journal	August 2011

Cited By (3)

Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes metastasis Strilic, Boris; Yang, Lida; Albarrán-Juárez, Julián Nature, Vol. 536, Issue 7615 https://doi.org/10.1038/nature19076	journal	August 2016
Not just amyloid: physiological functions of the amyloid precursor protein family Müller, Ulrike C.; Deller, Thomas; Korte, Martin Nature Reviews Neuroscience, Vol. 18, Issue 5 https://doi.org/10.1038/nrn.2017.29	journal	March 2017
HIV-1 counteracts an innate restriction by amyloid precursor protein resulting in neurodegeneration Chai, Qingqing; Jovasevic, Vladimir; Malikov, Viacheslav Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/s41467-017-01795-8	journal	November 2017

Similar Records

The amyloid precursor protein and postnatal neurogenesis/neuroregeneration

Journal Article · Fri Mar 03 00:00:00 EST 2006 · Biochemical and Biophysical Research Communications · OSTI ID:1178473

Yanan, Chen; Tang, Bor Luen

Interaction of the amyloid precursor protein-like protein 1 (APLP1) E2 domain with heparan sulfate involves two distinct binding modes

Journal Article · Sun Mar 01 00:00:00 EST 2015 · Acta Crystallographica. Section D: Biological Crystallography · OSTI ID:1178473

Mayer, Magnus C.; Roeser, Dirk; Multhaup, Gerd

beta. -Amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues

Journal Article · Sat Oct 01 00:00:00 EDT 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA) · OSTI ID:1178473

Selkoe, D J; Podlisny, M B; Joachim, C L; +4 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
amyloid precursor protein
crystal structure
death receptor 6
dimerization
signal activation

Title: The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation

Citation Formats

References (29)

Cited By (3)

Similar Records

Related Subjects