title: The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation.
abstract: 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.
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA;
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.affiliation: Laboratory of Brain Development and Repair, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Olav
authors.initials: O
authors.lastname: Olsen
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA;
authors.forename: Dorothea
authors.initials: D
authors.lastname: Tzvetkova-Robev
authors.affiliation: Laboratory of Brain Development and Repair, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Tessier-Lavigne
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA; nikolovd@mskcc.org.
authors.forename: Dimitar B
authors.initials: DB
authors.lastname: Nikolov
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D003460:Crystallization; D019281:Dimerization; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016564:Amyloid beta-Protein Precursor; D018124:Receptors, Tumor Necrosis Factor; C485251:Tnfrsf21 protein, mouse
keywords: amyloid precursor protein; crystal structure; death receptor 6; dimerization; signal activation
references.citation: Nat Med. 2000 Apr;6(4):397-404
references.pmid: 10742146
references.citation: Microsc Res Tech. 2000 Aug 1;50(3):184-95
references.pmid: 10891884
references.citation: Nature. 2001 Dec 6;414(6864):643-8
references.pmid: 11740561
references.citation: Mol Cell. 2004 Aug 13;15(3):343-53
references.pmid: 15304215
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references.pmid: 15572765
references.citation: J Neurosci. 2006 Jul 5;26(27):7212-21
references.pmid: 16822978
references.citation: Acta Crystallogr D Biol Crystallogr. 2007 Jan;63(Pt 1):32-41
references.pmid: 17164524
references.citation: Cytokine. 2007 Feb;37(2):101-7
references.pmid: 17449269
references.citation: Nature. 2009 Feb 19;457(7232):981-9
references.pmid: 19225519
references.citation: J Neurosci. 2009 Aug 19;29(33):10405-9
references.pmid: 19692615
references.citation: J Neurosci. 2009 Sep 2;29(35):10788-801
references.pmid: 19726636
references.citation: J Biol Chem. 2010 Jan 15;285(3):2165-73
references.pmid: 19906646
references.citation: Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
references.pmid: 20124702
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5381-6
references.pmid: 20212142
references.citation: J Mol Biol. 2011 Jun 3;409(2):189-201
references.pmid: 21463639
references.citation: Biochemistry. 2011 Jun 21;50(24):5453-64
references.pmid: 21574595
references.citation: Cold Spring Harb Perspect Biol. 2011 Jul 01;3(7):null
references.pmid: 21576255
references.citation: J Biol Chem. 2011 Aug 26;286(34):29748-57
references.pmid: 21715329
references.citation: Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16229-34
references.pmid: 21930949
references.citation: J Mol Biol. 2012 Feb 24;416(3):438-52
references.pmid: 22245578
references.citation: Acta Crystallogr D Biol Crystallogr. 2012 May;68(Pt 5):521-30
references.pmid: 22525750
references.citation: Annu Rev Med. 2013;64:367-83
references.pmid: 23327526
references.citation: PLoS One. 2013 Dec 04;8(12):e81926
references.pmid: 24324731
references.citation: FEBS Lett. 2014 Jan 31;588(3):401-7
references.pmid: 24374337
references.citation: Biol Chem. 2014 May;395(5):485-98
references.pmid: 24516000
references.citation: J Neurosci. 2014 May 7;34(19):6425-37
references.pmid: 24806669
references.citation: J Neurosci. 2014 May 7;34(19):6438-47
references.pmid: 24806670
references.citation: J Struct Biol. 2014 Jul;187(1):30-37
references.pmid: 24859793
references.citation: Methods Enzymol. 1997;276:307-26
references.pmid: 27754618
references.citation: FEBS Lett. 1998 Jul 24;431(3):351-6
references.pmid: 9714541