期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 15, 期 8, 页码 849-857出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1457
关键词
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资金
- Biotechnology and Biological Sciences Research Council [E002285/1, C503162/1, BB/C503162/1] Funding Source: Medline
- Medical Research Council [G0400775, G0400389(70832), G78/7267, G0400775(71657), G0500367, G000164, G0400389] Funding Source: Medline
- Wellcome Trust [078765, 077082, 079440] Funding Source: Medline
- Biotechnology and Biological Sciences Research Council [BB/C503162/1] Funding Source: researchfish
- Medical Research Council [G0500367, G0400775, G0400389] Funding Source: researchfish
- MRC [G0400389, G0400775, G0500367] Funding Source: UKRI
The Notch receptor and its ligands are key components in a core metazoan signaling pathway that regulates the spatial patterning, timing and outcome of many cell-fate decisions. Ligands contain a disulfide-rich Delta/Serrate/LAG-2 (DSL) domain required for Notch trans-activation or cis-inhibition. Here we report the X-ray structure of a receptor binding region of a Notch ligand, the DSL-EGF3 domains of human Jagged-1 (J-1(DSL-EGF3)). The structure reveals a highly conserved face of the DSL domain, and we show, by functional analysis of Drosophila melanogster ligand mutants, that this surface is required for both cis- and trans-regulatory interactions with Notch. We also identify, using NMR, a surface of Notch-1 involved in J-1(DSL-EGF3) binding. Our data imply that cis- and trans-regulation may occur through the formation of structurally distinct complexes that, unexpectedly, involve the same surfaces on both ligand and receptor.
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