Structural characterization of the self-association of the death domain of p75(NTR.).

The neurotrophin receptor p75(NTR) conveys multiple signals via its intracellular death domain. However, how the death domain is activated and interacts with downstream adaptors remains unclear. Here, we report two crystal structures of the p75(NTR) death domain in the form of a non-covalent asymmet...

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Main Authors: Qianhui Qu, Jun Chen, Yizhi Wang, Wenjun Gui, Li Wang, Zusen Fan, Tao Jiang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3589453?pdf=render
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author Qianhui Qu
Jun Chen
Yizhi Wang
Wenjun Gui
Li Wang
Zusen Fan
Tao Jiang
author_facet Qianhui Qu
Jun Chen
Yizhi Wang
Wenjun Gui
Li Wang
Zusen Fan
Tao Jiang
author_sort Qianhui Qu
collection DOAJ
description The neurotrophin receptor p75(NTR) conveys multiple signals via its intracellular death domain. However, how the death domain is activated and interacts with downstream adaptors remains unclear. Here, we report two crystal structures of the p75(NTR) death domain in the form of a non-covalent asymmetric dimer and a Cys379-Cys379 disulfide bond linked symmetric dimer, respectively. These two dimer arrangements have not previously been observed in other death domain-containing proteins. Further analysis shows that both the Cys379-Cys379 disulfide linked and non-covalent full-length p75(NTR) dimers are present on the cell surface. These observations suggest that various oligomers may exist simultaneously on the cell surface, and that p75(NTR) activation and signalling may be modulated by neurotrophins or other factors via inducing a shift of the equilibrium between different oligomeric states.
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spelling doaj.art-3638e4fd58944d64817e445c90f1e31d2022-12-21T17:56:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5783910.1371/journal.pone.0057839Structural characterization of the self-association of the death domain of p75(NTR.).Qianhui QuJun ChenYizhi WangWenjun GuiLi WangZusen FanTao JiangThe neurotrophin receptor p75(NTR) conveys multiple signals via its intracellular death domain. However, how the death domain is activated and interacts with downstream adaptors remains unclear. Here, we report two crystal structures of the p75(NTR) death domain in the form of a non-covalent asymmetric dimer and a Cys379-Cys379 disulfide bond linked symmetric dimer, respectively. These two dimer arrangements have not previously been observed in other death domain-containing proteins. Further analysis shows that both the Cys379-Cys379 disulfide linked and non-covalent full-length p75(NTR) dimers are present on the cell surface. These observations suggest that various oligomers may exist simultaneously on the cell surface, and that p75(NTR) activation and signalling may be modulated by neurotrophins or other factors via inducing a shift of the equilibrium between different oligomeric states.http://europepmc.org/articles/PMC3589453?pdf=render
spellingShingle Qianhui Qu
Jun Chen
Yizhi Wang
Wenjun Gui
Li Wang
Zusen Fan
Tao Jiang
Structural characterization of the self-association of the death domain of p75(NTR.).
PLoS ONE
title Structural characterization of the self-association of the death domain of p75(NTR.).
title_full Structural characterization of the self-association of the death domain of p75(NTR.).
title_fullStr Structural characterization of the self-association of the death domain of p75(NTR.).
title_full_unstemmed Structural characterization of the self-association of the death domain of p75(NTR.).
title_short Structural characterization of the self-association of the death domain of p75(NTR.).
title_sort structural characterization of the self association of the death domain of p75 ntr
url http://europepmc.org/articles/PMC3589453?pdf=render
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