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Delta-like 1 and Delta-like 4 differently require their extracellular domains for triggering Notch signaling in mice
Delta-like (Dll) 1 and Dll4 differently function as Notch ligands in a context-dependent manner. As these ligands share structural properties, the molecular basis for their functional difference is poorly understood. Here, we investigated the superiority of Dll4 over Dll1 with respect to induction o...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986876/ https://www.ncbi.nlm.nih.gov/pubmed/31934853 http://dx.doi.org/10.7554/eLife.50979 |
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author | Hirano, Ken-ichi Suganami, Akiko Tamura, Yutaka Yagita, Hideo Habu, Sonoko Kitagawa, Motoo Sato, Takehito Hozumi, Katsuto |
author_facet | Hirano, Ken-ichi Suganami, Akiko Tamura, Yutaka Yagita, Hideo Habu, Sonoko Kitagawa, Motoo Sato, Takehito Hozumi, Katsuto |
author_sort | Hirano, Ken-ichi |
collection | PubMed |
description | Delta-like (Dll) 1 and Dll4 differently function as Notch ligands in a context-dependent manner. As these ligands share structural properties, the molecular basis for their functional difference is poorly understood. Here, we investigated the superiority of Dll4 over Dll1 with respect to induction of T cell development using a domain-swapping approach in mice. The DOS motif, shared by Notch ligands—except Dll4—contributes to enhancing the activity of Dll for signal transduction. The module at the N-terminus of Notch ligand (MNNL) of Dll4 is inherently advantageous over Dll1. Molecular dynamic simulation revealed that the loop structure in MNNL domain of Dll1 contains unique proline residues with limited range of motion. The Dll4 mutant with Dll1-derived proline residues showed reduced activity. These results suggest that the loop structure—present within the MNNL domain—with a wide range of motion ensures the superiority of Dll4 and uniquely contributes to the triggering of Notch signaling. |
format | Online Article Text |
id | pubmed-6986876 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-69868762020-01-30 Delta-like 1 and Delta-like 4 differently require their extracellular domains for triggering Notch signaling in mice Hirano, Ken-ichi Suganami, Akiko Tamura, Yutaka Yagita, Hideo Habu, Sonoko Kitagawa, Motoo Sato, Takehito Hozumi, Katsuto eLife Developmental Biology Delta-like (Dll) 1 and Dll4 differently function as Notch ligands in a context-dependent manner. As these ligands share structural properties, the molecular basis for their functional difference is poorly understood. Here, we investigated the superiority of Dll4 over Dll1 with respect to induction of T cell development using a domain-swapping approach in mice. The DOS motif, shared by Notch ligands—except Dll4—contributes to enhancing the activity of Dll for signal transduction. The module at the N-terminus of Notch ligand (MNNL) of Dll4 is inherently advantageous over Dll1. Molecular dynamic simulation revealed that the loop structure in MNNL domain of Dll1 contains unique proline residues with limited range of motion. The Dll4 mutant with Dll1-derived proline residues showed reduced activity. These results suggest that the loop structure—present within the MNNL domain—with a wide range of motion ensures the superiority of Dll4 and uniquely contributes to the triggering of Notch signaling. eLife Sciences Publications, Ltd 2020-01-16 /pmc/articles/PMC6986876/ /pubmed/31934853 http://dx.doi.org/10.7554/eLife.50979 Text en © 2020, Hirano et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Hirano, Ken-ichi Suganami, Akiko Tamura, Yutaka Yagita, Hideo Habu, Sonoko Kitagawa, Motoo Sato, Takehito Hozumi, Katsuto Delta-like 1 and Delta-like 4 differently require their extracellular domains for triggering Notch signaling in mice |
title | Delta-like 1 and Delta-like 4 differently require their extracellular domains for triggering Notch signaling in mice |
title_full | Delta-like 1 and Delta-like 4 differently require their extracellular domains for triggering Notch signaling in mice |
title_fullStr | Delta-like 1 and Delta-like 4 differently require their extracellular domains for triggering Notch signaling in mice |
title_full_unstemmed | Delta-like 1 and Delta-like 4 differently require their extracellular domains for triggering Notch signaling in mice |
title_short | Delta-like 1 and Delta-like 4 differently require their extracellular domains for triggering Notch signaling in mice |
title_sort | delta-like 1 and delta-like 4 differently require their extracellular domains for triggering notch signaling in mice |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986876/ https://www.ncbi.nlm.nih.gov/pubmed/31934853 http://dx.doi.org/10.7554/eLife.50979 |
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