Structural basis for Ccd1 auto-inhibition in the Wnt pathway through homomerization of the DIX domain
| العنوان: | Structural basis for Ccd1 auto-inhibition in the Wnt pathway through homomerization of the DIX domain |
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| المؤلفون: | Kensuke Shiomi, Masayuki Masu, Kaori Wakamatsu, Shohei Fujita, Naoki Shibata, Takuya Katsutani, Kazuko Keino-Masu, Shin-ichi Terawaki, Yoshiki Higuchi |
| المصدر: | Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) Scientific Reports |
| بيانات النشر: | Nature Portfolio, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Models, Molecular, 0301 basic medicine, Protein Conformation, Science, Stimulation, Cell fate determination, medicine.disease_cause, Bioinformatics, Article, Protein filament, Mice, Structure-Activity Relationship, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Protein Interaction Domains and Motifs, Amino Acid Sequence, Wnt Signaling Pathway, Zebrafish, chemistry.chemical_classification, Mutation, Binding Sites, Multidisciplinary, biology, Intracellular Signaling Peptides and Proteins, Wnt signaling pathway, biology.organism_classification, Dishevelled, Cell biology, 030104 developmental biology, chemistry, Domain (ring theory), Medicine, Protein Multimerization, 030217 neurology & neurosurgery, Protein Binding |
| الوصف: | Wnt signaling plays an important role in governing cell fate decisions. Coiled-coil-DIX1 (Ccd1), Dishevelled (Dvl), and Axin are signaling proteins that regulate the canonical pathway by controlling the stability of a key signal transducer β-catenin. These proteins contain the DIX domain with a ubiquitin-like fold, which mediates their interaction in the β-catenin destruction complex through dynamic head-to-tail polymerization. Despite high sequence similarities, mammalian Ccd1 shows weaker stimulation of β-catenin transcriptional activity compared with zebrafish (z) Ccd1 in cultured cells. Here, we show that the mouse (m) Ccd1 DIX domain displays weaker ability for homopolymerization than that of zCcd1. Furthermore, X-ray crystallographic analysis of mCcd1 and zCcd1 DIX domains revealed that mCcd1 was assembled into a double-helical filament by the insertion of the β1-β2 loop into the head-to-tail interface, whereas zCcd1 formed a typical single-helical polymer similar to Dvl1 and Axin. The mutation in the contact interface of mCcd1 double-helical polymer changed the hydrodynamic properties of mCcd1 so that it acquired the ability to induce Wnt-specific transcriptional activity similar to zCcd1. These findings suggest a novel regulatory mechanism by which mCcd1 modulates Wnt signaling through auto-inhibition of dynamic head-to-tail homopolymerization. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::31bb98dc599b17c15df257a1e831755d https://doaj.org/article/82ea2c14f6a04fdfac2aa1e522bd3b63 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....31bb98dc599b17c15df257a1e831755d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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