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:
-
- 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
- Publication Date:
- Research Org.:
- Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); National Inst. of Health (NIH) (United States)
- Contributing Org.:
- Rockefeller Univ., New York, NY (United States)
- OSTI Identifier:
- 1178473
- Grant/Contract Number:
- AC02-06CH11357; 1R01NS089786; P41 GM103403
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Genes & Development
- Additional Journal Information:
- Journal Volume: 29; Journal Issue: 8; Journal ID: ISSN 0890-9369
- Publisher:
- Cold Springs Harbor Press
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; amyloid precursor protein; crystal structure; death receptor 6; dimerization; signal activation
Citation Formats
Xu, Kai, Olsen, Olav, Tzvetkova-Robev, Dorothea, Tessier-Lavigne, Marc, and Nikolov, Dimitar B. The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation. United States: N. p., 2015.
Web. doi:10.1101/gad.257675.114.
Xu, Kai, Olsen, Olav, Tzvetkova-Robev, Dorothea, Tessier-Lavigne, Marc, & Nikolov, Dimitar B. The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation. United States. https://doi.org/10.1101/gad.257675.114
Xu, Kai, Olsen, Olav, Tzvetkova-Robev, Dorothea, Tessier-Lavigne, Marc, and Nikolov, Dimitar B. Thu .
"The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation". United States. https://doi.org/10.1101/gad.257675.114. https://www.osti.gov/servlets/purl/1178473.
@article{osti_1178473,
title = {The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation},
author = {Xu, Kai and Olsen, Olav and Tzvetkova-Robev, Dorothea and Tessier-Lavigne, Marc and Nikolov, Dimitar B.},
abstractNote = {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.},
doi = {10.1101/gad.257675.114},
journal = {Genes & Development},
number = 8,
volume = 29,
place = {United States},
year = {Thu Apr 02 00:00:00 EDT 2015},
month = {Thu Apr 02 00:00:00 EDT 2015}
}
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