与淀粉样前体蛋白结合的DR6晶体结构有助于深入了解死亡受体激活过程。

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

作者信息

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

机构信息

Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA;

Laboratory of Brain Development and Repair, The Rockefeller University, New York, New York 10065, USA.

出版信息

Genes Dev. 2015 Apr 15;29(8):785-90. doi: 10.1101/gad.257675.114. Epub 2015 Apr 2.

DOI:10.1101/gad.257675.114

PMID:25838500

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4403255/

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.

摘要

淀粉样前体蛋白（APP）因其与阿尔茨海默病的遗传关联而备受关注。死亡受体6（DR6）最近被证明可通过蛋白质细胞外区域与APP结合，刺激轴突修剪并抑制突触形成。在此，我们报道了与APP的E2结构域结合的DR6胞外结构域的晶体结构，并表明它支持APP诱导细胞表面DR6二聚化和激活的模型。

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J Neurosci. 2014 May 7;34(19):6425-37. doi: 10.1523/JNEUROSCI.4963-13.2014.

The structural biology of the amyloid precursor protein APP - a complex puzzle reveals its multi-domain architecture.

Biol Chem. 2014 May;395(5):485-98. doi: 10.1515/hsz-2013-0280.

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与淀粉样前体蛋白结合的DR6晶体结构有助于深入了解死亡受体激活过程。

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

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与淀粉样前体蛋白结合的DR6晶体结构有助于深入了解死亡受体激活过程。

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

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出版信息

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