2026-06-14T05:06:00Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/87252025-02-27T14:31:02Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617
Repisalud
author
Vilar, Marçal
author
Sung, Tsung-Chang
author
Chen, Zhijiang
author
Garcia-Carpio, Irmina
author
Fernandez, Eva M
author
Xu, Jiqing
author
Riek, Roland
author
Lee, Kuo-Fen
funder
Instituto de Salud Carlos III
funder
Ministerio de Economía y Competitividad (España)
2019-12-02T09:28:09Z
2019-12-02T09:28:09Z
2014-08
PLoS Biol. 2014 Aug 5;12(8):e1001918.
10.1371/journal.pbio.1001918
1545-7885
1545-7885
PLoS biology
25093680
http://hdl.handle.net/20.500.12105/8725
The p75 neurotrophin receptor, a member of the tumor necrosis factor receptor superfamily, is required as a co-receptor for the Nogo receptor (NgR) to mediate the activity of myelin-associated inhibitors such as Nogo, MAG, and OMgp. p45/NRH2/PLAIDD is a p75 homologue and contains a death domain (DD). Here we report that p45 markedly interferes with the function of p75 as a co-receptor for NgR. P45 forms heterodimers with p75 and thereby blocks RhoA activation and inhibition of neurite outgrowth induced by myelin-associated inhibitors. p45 binds p75 through both its transmembrane (TM) domain and DD. To understand the underlying mechanisms, we have determined the three-dimensional NMR solution structure of the intracellular domain of p45 and characterized its interaction with p75. We have identified the residues involved in such interaction by NMR and co-immunoprecipitation. The DD of p45 binds the DD of p75 by electrostatic interactions. In addition, previous reports suggested that Cys257 in the p75 TM domain is required for signaling. We found that the interaction of the cysteine 58 of p45 with the cysteine 257 of p75 within the TM domain is necessary for p45-p75 heterodimerization. These results suggest a mechanism involving both the TM domain and the DD of p45 to regulate p75-mediated signaling.
eng
Heterodimerization of p45-p75 modulates p75 signaling: structural basis and mechanism of action
research article
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URL
https://repisalud.isciii.es/bitstreams/88b14015-4273-4942-9fe5-a7d6a70d3b23/download
File
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application/pdf
HeterodimerizationOfP45P75_2014.pdf
URL
https://repisalud.isciii.es/bitstreams/6f97f504-a931-4dac-8f25-cc953b970888/download
File
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text/plain
HeterodimerizationOfP45P75_2014.pdf.txt